_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e10
_enti_e2
_enti_e3
_enti_e4
_enti_e55
_enti_e53
_enti_e59
_enti_e51
_enti_e50
_enti_e54
_enti_e56
_enti_e52
_enti_e58
_enti_e57
_enti_e61
_enti_e62
_enti_e60
g2_fact_g2
g1_fact_g1
g2_fact_g12
g2_fact_g13
g1_fact_g14
p1_propro_p1
PMID: 18226603, 11899233, 7541421
The SR most associated with AM silica binding are SR-AI, SR-AII, and MARCO.
c1 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
c2 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 18226603, 11899233, 7541421
The SR most associated with AM silica binding are SR-AI, SR-AII, and MARCO.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 18226603, 11899233, 7541421
The SR most associated with AM silica binding are SR-AI, SR-AII, and MARCO.
PMID: 18226603, 17405873
Ojala et al. propose that multiple MARCO receptors can group together on the surface of the cell, allowing the SRCR regions to dimerize or oligomerize, creating a much larger binding surface area that is capable of binding physically large ligands such as silica and bacteria.
c8 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c7 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 18226603, 17405873
Ojala et al. propose that multiple MARCO receptors can group together on the surface of the cell, allowing the SRCR regions to dimerize or oligomerize, creating a much larger binding surface area that is capable of binding physically large ligands such as silica and bacteria.
c9 cso30:c:InputProcess connector
c10 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 18226603, 7541421
Another unresolved issue with the receptor-mediated hypothesis is that nontoxic particles such as titanium dioxide are known to bind to the same receptors without triggering the death response.
c12 cso30:c:InputProcess connector
c15 cso30:c:InputProcess connector
c19 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 18226603, 7541421
Another unresolved issue with the receptor-mediated hypothesis is that nontoxic particles such as titanium dioxide are known to bind to the same receptors without triggering the death response.
c13 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c16 cso30:c:OutputProcess connector
p7_propro_p7
PMID: 18226603, 7541421
Another unresolved issue with the receptor-mediated hypothesis is that nontoxic particles such as titanium dioxide are known to bind to the same receptors without triggering the death response.
c14 cso30:c:InputProcess connector
c18 cso30:c:InputProcess connector
c20 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 18226603, 11785981
One study, using a synthetic bovine SR-A construct, demonstrated that heat-shock proteins HSP90 and HSP70, in addition to glyceraldehyde-3-phosphate dehydrogenase, bound to the cytoplasmic N-terminus of the SR.
c21 cso30:c:InputProcess connector
c26 cso30:c:InputProcess connector
c27 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 18226603, 11785981
One study, using a synthetic bovine SR-A construct, demonstrated that heat-shock proteins HSP90 and HSP70, in addition to glyceraldehyde-3-phosphate dehydrogenase, bound to the cytoplasmic N-terminus of the SR.
c22 cso30:c:InputProcess connector
c24 cso30:c:InputProcess connector
c25 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 18226603, 11785981
One study, using a synthetic bovine SR-A construct, demonstrated that heat-shock proteins HSP90 and HSP70, in addition to glyceraldehyde-3-phosphate dehydrogenase, bound to the cytoplasmic N-terminus of the SR.
c23 cso30:c:InputProcess connector
c28 cso30:c:InputProcess connector
c29 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 18226603, 9422792
Hsu et al. found that SR-A ligand-induced tyrosine phosphorylation followed by activation of protein kinase C (PKC) resulted in urokinase-type plasminogen activator expression in THP-1 cells.
c30 cso30:c:InputAssociation connector
c31 cso30:c:InputProcess connector
c32 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 18226603, 9422792
Hsu et al. found that SR-A ligand-induced tyrosine phosphorylation followed by activation of protein kinase C (PKC) resulted in urokinase-type plasminogen activator expression in THP-1 cells.
c33 cso30:c:InputAssociation connector
c34 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 18226603, 12626342
In a related topic, crocidolite asbestos has also been shown to trigger the PKC (delta isoform specific) pathway leading to apoptosis, but it was not linked with SR activation.
c35 cso30:c:InputProcess connector
c37 cso30:c:InputAssociation connector
c36 cso30:c:OutputProcess connector
p14_propro_p14
PMID: 18226603, 12626342
In a related topic, crocidolite asbestos has also been shown to trigger the PKC (delta isoform specific) pathway leading to apoptosis, but it was not linked with SR activation.
c38 cso30:c:InputAssociation connector
p15_propro_p15
PMID: 18226603, 10593991
Fong and Le identified serine phosphorylation after ac-LDL stimulation that could be disrupted using SR-A receptor mutants on CHO and COS cells at the Ser49 and Asp25 amino acid sites.
c39 cso30:c:InputProcess connector
c41 cso30:c:InputAssociation connector
c40 cso30:c:OutputProcess connector
p16_propro_p16
PMID: 18226603, 11390374
In a study by Hsu et al., it was demonstrated that two different SR-A ligands (ox-LDL and fucoidan) could trigger differential cell responses using slightly different protein kinase signaling pathways.
c42 cso30:c:InputProcess connector
c43 cso30:c:InputProcess connector
c44 cso30:c:OutputProcess connector
p17_propro_p17
PMID: 18226603, 11390374
In a study by Hsu et al., it was demonstrated that two different SR-A ligands (ox-LDL and fucoidan) could trigger differential cell responses using slightly different protein kinase signaling pathways.
c45 cso30:c:InputProcess connector
c46 cso30:c:InputProcess connector
c47 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 18226603, 15218052
For example, the presence of TLR-4 has been shown to be important for the induction of MARCO expression using TLR-4 mutant mice.
c49 cso30:c:InputAssociation connector
c48 cso30:c:OutputProcess connector
p19_propro_p19
PMID: 18226603, 16339540
In addition, MARCO-null mice were associated with inhibited IL-12 production, whereas SR-A-null mice were associated with enhanced IL-12 production compared to wild-type mice in response to lipopolysaccharide (LPS) or IFN-gamma.
c51 cso30:c:InputAssociation connector
c56 cso30:c:InputAssociation connector
c58 cso30:c:InputInhibitor connector
c54 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 18226603, 16339540
In addition, MARCO-null mice were associated with inhibited IL-12 production, whereas SR-A-null mice were associated with enhanced IL-12 production compared to wild-type mice in response to lipopolysaccharide (LPS) or IFN-gamma.
c50 cso30:c:InputAssociation connector
c60 cso30:c:InputInhibitor connector
c59 cso30:c:OutputProcess connector
p21_propro_p21
PMID: 18226603, 16339540
In addition, MARCO-null mice were associated with inhibited IL-12 production, whereas SR-A-null mice were associated with enhanced IL-12 production compared to wild-type mice in response to lipopolysaccharide (LPS) or IFN-gamma.
c53 cso30:c:InputAssociation connector
c55 cso30:c:InputAssociation connector
c57 cso30:c:InputInhibitor connector
c52 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 18226603, 11570673
Adhesion protein ICAM-1, although not directly involved in silica uptake, is upregulated on AM and other cell types with in vivo and in vitro silica exposure and believed to initiate the inflammatory PMN influx into the lungs.
c61 cso30:c:InputAssociation connector
c62 cso30:c:OutputProcess connector
p23_propro_p23
PMID: 18226603, 12788471
There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical)
PMID: 18226603, 10516215
It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.
c67 cso30:c:InputAssociation connector
c162 cso30:c:InputInhibitor connector
c63 cso30:c:OutputProcess connector
p24_propro_p24
PMID: 18226603, 12788471
There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical)
PMID: 18226603, 10516215
It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.
c68 cso30:c:InputAssociation connector
c161 cso30:c:InputInhibitor connector
c64 cso30:c:OutputProcess connector
p25_propro_p25
PMID: 18226603, 12788471
There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical)
c69 cso30:c:InputAssociation connector
c65 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 18226603, 12788471
There are several possible sources of free radicals resulting from silica internalization, including particle-derived reactive oxygen species (ROS), cell-derived ROS and reactive nitrogen species (RNS), and the interaction of particle- and cell-derived free radicals producing peroxynitrite (ONOOO2radical) from nitric oxide (NOradical) and superoxide anion (O2radical)
c70 cso30:c:InputAssociation connector
c75 cso30:c:InputAssociation connector
c76 cso30:c:InputAssociation connector
c79 cso30:c:InputAssociation connector
c80 cso30:c:InputAssociation connector
c66 cso30:c:OutputProcess connector
p27_propro_p27
PMID: 18226603, 7705309
In addition, the AM process of silica phagocytosis has been reported to produce O2radical, hydrogen peroxide (H2O2), and hydroxyl radicals (HOradical)
c71 cso30:c:InputAssociation connector
c73 cso30:c:OutputProcess connector
p28_propro_p28
PMID: 18226603, 7705309
In addition, the AM process of silica phagocytosis has been reported to produce O2radical, hydrogen peroxide (H2O2), and hydroxyl radicals (HOradical)
c72 cso30:c:InputAssociation connector
c74 cso30:c:OutputProcess connector
p29_propro_p29
PMID: 18226603, 7705309
In addition, the AM process of silica phagocytosis has been reported to produce O2radical, hydrogen peroxide (H2O2), and hydroxyl radicals (HOradical)
PMID: 18226603
The hydroxyl radical is the most potentially damaging ROS (due to very short half-life, high reactivity, and lack of effective elimination) to the lung, but it is produced to any significant degree only in the presence of contaminants such as iron (Fenton reaction).
c77 cso30:c:InputAssociation connector
c127 cso30:c:InputAssociation connector
c78 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 18226603, 8603472, 8394268, 7705289
Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo.
PMID: 18226603, 10516215
It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.
c82 cso30:c:InputAssociation connector
c164 cso30:c:InputInhibitor connector
p32_propro_p32
PMID: 18226603, 11570678, 10963957, 15242185
Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo.
c83 cso30:c:InputAssociation connector
p33_propro_p33
PMID: 18226603, 11570678, 10963957, 15242185
Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo.
c84 cso30:c:InputAssociation connector
p35_propro_p35
PMID: 18226603, 10471390
For example, silica-induced free radicals activated MEK and ERK phosphorylation in a rat fibroblast cell line.
PMID: 18226603
For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).
c87 cso30:c:InputProcess connector
c85 cso30:c:InputAssociation connector
c88 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 18226603, 10471390
For example, silica-induced free radicals activated MEK and ERK phosphorylation in a rat fibroblast cell line.
PMID: 18226603
For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).
c89 cso30:c:InputProcess connector
c86 cso30:c:InputAssociation connector
c90 cso30:c:OutputProcess connector
p37_propro_p37
PMID: 18226603, 10521445
Luciferase reporter mice have also been used to show AP-1 activation in vivo after silica inhalation through ERK and p38 MAPK signaling pathways.
c93 cso30:c:InputProcess connector
c95 cso30:c:InputAssociation connector
c94 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 18226603, 10521445
Luciferase reporter mice have also been used to show AP-1 activation in vivo after silica inhalation through ERK and p38 MAPK signaling pathways.
PMID: 18226603, 11280724
In vitro evidence for silica-initiated oxidative stress-induced AP-1 activation associated with JNK signaling, via c-Jun-NH2-terminal amino kinases, can be found in Shukla et al.
PMID: 18226603
For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).
c96 cso30:c:InputAssociation connector
c97 cso30:c:InputProcess connector
c102 cso30:c:InputAssociation connector
c98 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 18226603, 11280724
In vitro evidence for silica-initiated oxidative stress-induced AP-1 activation associated with JNK signaling, via c-Jun-NH2-terminal amino kinases, can be found in Shukla et al.
c99 cso30:c:InputAssociation connector
c100 cso30:c:InputProcess connector
c101 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 18226603
For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).
c91 cso30:c:InputAssociation connector
c92 cso30:c:InputProcess connector
c103 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 18226603, 17158358
In a rat AM model, Liu et al. demonstrated that TNF-alpha and IL-1beta release after silica exposure was mediated through phosphatidylcholine-specific phospholipase C regulated in a redox-dependent fashion.
c104 cso30:c:InputProcess connector
c106 cso30:c:InputAssociation connector
c105 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 18226603, 17158358
In a rat AM model, Liu et al. demonstrated that TNF-alpha and IL-1beta release after silica exposure was mediated through phosphatidylcholine-specific phospholipase C regulated in a redox-dependent fashion.
PMID: 18226603
For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).
c110 cso30:c:InputAssociation connector
c112 cso30:c:InputAssociation connector
c114 cso30:c:InputAssociation connector
c108 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 18226603, 17158358
In a rat AM model, Liu et al. demonstrated that TNF-alpha and IL-1beta release after silica exposure was mediated through phosphatidylcholine-specific phospholipase C regulated in a redox-dependent fashion.
PMID: 18226603
For example, SR may be the way silica binds to the AM initially, followed by particle endocytosis complete with a respiratory burst creating ROS and RNS, followed by PKC-mediated MAP kinase signaling cascades resulting in AP-1 and NF-kappaB activation, which ultimately results in cytokine release (IL-1beta, MIP-1, MCP-1, and TNF-alpha).
c109 cso30:c:InputAssociation connector
c111 cso30:c:InputAssociation connector
c113 cso30:c:InputAssociation connector
c107 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 18226603, 10438654, 9747602
The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].
c116 cso30:c:InputAssociation connector
c123 cso30:c:InputAssociation connector
c115 cso30:c:OutputProcess connector
p44_propro_p44
PMID: 18226603, 10438654, 9747602
The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].
c117 cso30:c:InputAssociation connector
c124 cso30:c:InputAssociation connector
c118 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 18226603, 10438654, 9747602
The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].
c120 cso30:c:InputAssociation connector
c125 cso30:c:InputAssociation connector
c119 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 18226603, 10438654, 9747602
The inflammatory cytokines most commonly associated with silica-induced free radicals are TNF-alpha, IL-1beta, MIP-1, MIP-2, MCP-1 [103], and IL-8 (after TNF-alpha priming) [104].
c122 cso30:c:InputAssociation connector
c126 cso30:c:InputAssociation connector
c121 cso30:c:OutputProcess connector
p47_propro_p47
PMID: 18226603, 8277518
The untreated silica caused a significant reduction in lysosomal enzyme (cathepsin B) activity that was inhibited by silica pretreatment with dipalmitoyl lecithin or the presence of ammonium chloride.
c130 cso30:c:InputInhibitor connector
c132 cso30:c:InputInhibitor connector
c128 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 18226603, 8277518
The untreated silica caused a significant reduction in lysosomal enzyme (cathepsin B) activity that was inhibited by silica pretreatment with dipalmitoyl lecithin or the presence of ammonium chloride.
c131 cso30:c:InputInhibitor connector
c133 cso30:c:InputInhibitor connector
c129 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 18226603, 12781626, 11275417
Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].
c140 cso30:c:InputAssociation connector
c134 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 18226603, 12781626, 11275417
Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].
c141 cso30:c:InputAssociation connector
c135 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 18226603, 10969075, 10749748, 12611476
Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].
c142 cso30:c:InputAssociation connector
c136 cso30:c:OutputProcess connector
p52_propro_p52
PMID: 18226603, 10969075, 10749748, 12611476
Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].
c143 cso30:c:InputAssociation connector
c137 cso30:c:OutputProcess connector
p53_propro_p53
PMID: 18226603, 8968411, 11218049
Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].
c144 cso30:c:InputAssociation connector
c138 cso30:c:OutputProcess connector
p54_propro_p54
PMID: 18226603, 8968411, 11218049
Several other studies found silica-induced increases in PL and SP [17] and [18], including specific increases in SP-A [19] and [20], SP-D [19] and [21], vitamin E [22], and phosphatidyl inositol [23].
c145 cso30:c:InputAssociation connector
c139 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 18226603, 11218049
In contrast, Seiler et al. found a dose-dependent decrease in phosphatidyl glycerol in response to silica.
c147 cso30:c:InputAssociation connector
c146 cso30:c:OutputProcess connector
p56_propro_p56
PMID: 18226603, 11437644
Further evidence from the same group determined that the SR-A blocking antibody (2F-8) could significantly attenuate caspase activity after silica exposure in murine MH-S cells.
c148 cso30:c:InputProcess connector
c149 cso30:c:InputProcess connector
c150 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 18226603, 11437644
Further evidence from the same group determined that the SR-A blocking antibody (2F-8) could significantly attenuate caspase activity after silica exposure in murine MH-S cells.
c151 cso30:c:InputProcess connector
c153 cso30:c:InputInhibitor connector
c152 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 18226603, 16984918
Studies using MARCO/, SR-AI/II/, and CD36/ single and double null combinations on the C57BL/6 mouse model demonstrated that MARCO was exclusively associated with in vitro silica-induced AM apoptosis and cytotoxicity, in addition to silica binding and uptake.
c154 cso30:c:InputAssociation connector
p59_propro_p59
PMID: 18226603, 1323223, 1316905
Further evidence for silica-induced ROS in rat model lungs comes from observed increases in antioxidant enzymes such as manganese superoxide dismutase (MnSOD) from type II epithelial cells [90], along with increased SOD and glutathione peroxidase mRNA in rat lungs after silica inhalation.
c156 cso30:c:InputAssociation connector
c160 cso30:c:OutputProcess connector
p60_propro_p60
PMID: 18226603, 1323223, 1316905
Further evidence for silica-induced ROS in rat model lungs comes from observed increases in antioxidant enzymes such as manganese superoxide dismutase (MnSOD) from type II epithelial cells [90], along with increased SOD and glutathione peroxidase mRNA in rat lungs after silica inhalation.
c157 cso30:c:InputAssociation connector
c158 cso30:c:OutputProcess connector
p61_propro_p61
PMID: 18226603, 1323223, 1316905
Further evidence for silica-induced ROS in rat model lungs comes from observed increases in antioxidant enzymes such as manganese superoxide dismutase (MnSOD) from type II epithelial cells [90], along with increased SOD and glutathione peroxidase mRNA in rat lungs after silica inhalation.
c155 cso30:c:InputAssociation connector
c159 cso30:c:OutputProcess connector
p62_propro_p62
PMID: 18226603, 15893544
Both ex vivo exposures of AM and in vitro exposures of bone-marrow-derived macrophages to silica in the murine model have shown increased (relative to basal production) lymphocyte cytokines (IL-13 and IFN-gamma) using an antigen-presenting cell (APC) assay in macrophage/lymphocyte cocultures.
c166 cso30:c:InputAssociation connector
c165 cso30:c:OutputProcess connector
p63_propro_p63
PMID: 18226603, 15893544
Both ex vivo exposures of AM and in vitro exposures of bone-marrow-derived macrophages to silica in the murine model have shown increased (relative to basal production) lymphocyte cytokines (IL-13 and IFN-gamma) using an antigen-presenting cell (APC) assay in macrophage/lymphocyte cocultures.
PMID: 18226603, 11570676
This result was supported by another study using human AM exposed in vitro to silica, resulting in increased lymphocyte cytokines (IL-4 and IFN-gamma), using a human APC cell culture model.
c167 cso30:c:InputAssociation connector
c168 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 18226603, 11570676
This result was supported by another study using human AM exposed in vitro to silica, resulting in increased lymphocyte cytokines (IL-4 and IFN-gamma), using a human APC cell culture model.
c170 cso30:c:InputAssociation connector
c169 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 18226603, 12857937
This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.
c171 cso30:c:InputProcess connector
c173 cso30:c:InputAssociation connector
c172 cso30:c:OutputProcess connector
p31_propro_p31
PMID: 18226603, 8603472, 8394268, 7705289
Evidence strongly suggests that silica-derived ROS are directly responsible for in vitro DNA damage [81], [82] and [83], various morphological changes including apoptosis in in vitro cell cultures [79], [84] and [85], and acute lung damage in vivo.
PMID: 18226603, 10516215
It was also noted in this study that the GSH precursor (N-acetylcysteine) decreased ROS formation, resulting in reduced membrane permeability changes and DNA damage.
c163 cso30:c:InputInhibitor connector
c81 cso30:c:InputAssociation connector
p66_propro_p66
PMID: 18226603, 12857937
This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.
c174 cso30:c:InputProcess connector
c180 cso30:c:InputAssociation connector
c175 cso30:c:OutputProcess connector
p67_propro_p67
PMID: 18226603, 12857937
This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.
c176 cso30:c:InputProcess connector
c181 cso30:c:InputAssociation connector
c177 cso30:c:OutputProcess connector
p68_propro_p68
PMID: 18226603, 12857937
This study concluded that the apoptotic signaling pathway involved lysosomal leakage resulting in cathepsin D release, and acidic sphingomyelinase activation, which preceded the mitochondrial depolarization and caspase 3 and 9 activation (reported earlier by the same group) caused by silica exposure.
c178 cso30:c:InputProcess connector
c182 cso30:c:InputAssociation connector
c179 cso30:c:OutputProcess connector
p69_propro_p69
PMID: 18226603
This then leads to mitochondrial depolarization, caspase 3 and caspase 9 activation, and apoptosis.
c183 cso30:c:InputAssociation connector
c184 cso30:c:InputAssociation connector
silica_enti_e6
SiO2
silica
SR-A1_enti_MO000101490
SR-A1
SR-AII_enti_e5
SR-AII
MARCO_enti_MO000042355
MARCO
silica: SR-AII_enti_e11
SiO2
silica: SR-AII
silica: SR-A1_enti_e12
SiO2
silica: SR-A1
silica: MERCO_enti_e13
SiO2
silica: MERCO
MARCO: MARCO_enti_e16
MARCO: MARCO
titanium dioxide_enti_e17
titanium dioxide
titanium dioxide: SR-AII_enti_e18
titanium dioxide: SR-AII
titanium dioxide: SR-A1_enti_e19
titanium dioxide: SR-A1
titanium dioxide: MERCO_enti_e20
titanium dioxide: MERCO
Hsp90_enti_MO000021135
Hsp90
Hsp70_enti_MO000021614
Hsp70
GAPDH_enti_MO000066361
GAPDH
Hsp90: MSR_enti_e14
Hsp90: MSR
Hosp70: MSR_enti_e15
Hosp70: MSR
GAPDH: MSR_enti_e21
GAPDH: MSR
MSR_enti_e22
MSR
PKCdelta_enti_MO000017065
PKCdelta
PKCdelta{p}_enti_e23
PKCdelta{p}
urokinase-type plasminogen activator_enti_e24
urokinase-type plasminogen activator
crocidolite asbestos_enti_e25
crocidolite asbestos
SR-A1{pS}_enti_e26
SR-A1{pS}
oxLDL_enti_MO000107436
oxLDL
ac-LDL_enti_e28
ac-LDL
ox-LDL: SR-A1_enti_e29
ox-LDL: SR-A1
fucoidan: SR-A1_enti_e30
fucoidan: SR-A1
fucoidan_enti_e31
fucoidan
MARCO_enti_G013287
MARCO
TLR4 ligand: TLR4_enti_e33
TLR4 ligand: TLR4
LPS_enti_MO000016882
LPS
IFNgamma_enti_MO000016665
IFNgamma
IL-12 p40_enti_G010657
IL-12 p40
IL-12_enti_MO000017265
IL-12
ICAM-1_enti_MO000000306
ICAM-1
particle derived ROS_enti_MO000008272
particle derived ROS
cell-derived ROS_enti_e32
cell-derived ROS
RNS_enti_e34
RNS
peroxynitrite_enti_e35
peroxynitrite
hydrogen peroxide_enti_e37
hydrogen peroxide
nitric oxide_enti_e38
nitric oxide
superoxide anion_enti_e39
superoxide anion
hydroxyl radicals_enti_e36
hydroxyl radicals
MEK_enti_MO000000018
MEK
MEK{p}_enti_MO000038305
MEK{p}
ERK_enti_MO000000011
ERK
ERK{p}_enti_MO000038306
ERK{p}
p38_enti_MO000000022
p38
p38 {activated}_enti_e41
p38 {activated}
AP-1 {activated}_enti_MO000000276
AP-1 {activated}
AP-1_enti_e27
AP-1
JNK_enti_MO000000023
JNK
JNK {activated}_enti_e42
JNK {activated}
NF-kappaB_enti_MO000000058
NF-kappaB
NF-kappaB {activated}_enti_e40
NF-kappaB {activated}
TNF-alpha_enti_G010329
TNF-alpha
TNF-alpha_enti_MO000000289
TNF-alpha
IL-1beta_enti_G010389
IL-1beta
IL-1beta_enti_MO000016597
IL-1beta
phosphatidylcholine-specific phospholipase C_enti_e43
phosphatidylcholine-specific phospholipase C
phosphatidylcholine-specific phospholipase C {activated}_enti_e44
phosphatidylcholine-specific phospholipase C {activated}
MIP-1_enti_e45
MIP-1
MIP-1_enti_e46
MIP-1
MIP-2_enti_e47
MIP-2
MIP-2_enti_e48
MIP-2
MCP-1_enti_MO000017280
MCP-1
MCP1_enti_G010815
MCP1
IL-8_enti_MO000017264
IL-8
IL8_enti_e49
IL8
iron_enti_e64
Fe
iron
cathepsin B_enti_MO000042963
cathepsin B
dipalmitoyl lecithin_enti_e63
dipalmitoyl lecithin
ammonium chloride_enti_e65
ammonium chloride
surfactant protein_enti_e66
surfactant protein
phospholipids_enti_e67
phospholipids
SP-A_enti_e68
SP-A
SP-D_enti_e69
SP-D
vitamin E_enti_e70
vitamin E
phosphatidylinositide lipids_enti_MO000016797
phosphatidylinositide lipids
phosphatidyl glycerol_enti_e71
phosphatidyl glycerol
2F-8_enti_e72
2F-8
Caspases_enti_MO000016907
Caspases
2F-8: SR-A1_enti_e73
2F-8: SR-A1
Caspases {activated}_enti_e74
Caspases {activated}
SOD_enti_MO000021289
SOD
MnSOD_enti_e75
MnSOD
glutathione peroxidase_enti_e76
glutathione peroxidase
N-acetylcysteine_enti_e77
N-acetylcysteine
IL-13_enti_MO000007321
IL-13
IFNgamma {intracellular}_enti_e79
IFNgamma {intracellular}
IL-4_enti_MO000017053
IL-4
cathepsin D {extracellular}_enti_MO000081880
cathepsin D {extracellular}
cathepsin D_enti_e80
cathepsin D
A-SMase_enti_MO000017824
A-SMase
A-SMase {activated}_enti_e81
A-SMase {activated}
Caspase-3_enti_MO000016924
Caspase-3
Caspase-9_enti_MO000016987
Caspase-9
Caspase-3 {activated}_enti_e78
Caspase-3 {activated}
Caspase-9{activated}_enti_e82
Caspase-9{activated}