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Indirect
Indirect
Indirect
PMID: 18336664
Endotoxin/lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is an important activator of Kupffer cells, stimulating the production of inflammatory and fibrogeniccytokines, as well as reactive oxygen species (ROS).
PMID: 18336664, 9756487
One working model for the progression of alcoholic liver disease proposes that increased exposure of Kupffer cells to LPS during chronic ethanol consumption contributes to increased production of inflammatory mediators, in particular tumor necrosis factor TNF-alpha and ROS, leading to the progression of fatty liver, inflammation and fibrosis.
Indirect
Indirect
PMID: 18336664
Endotoxin/lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is an important activator of Kupffer cells, stimulating the production of inflammatory and fibrogeniccytokines, as well as reactive oxygen species (ROS).
PMID: 18336664, 16410364, 10961870, 15033490
Adiponectin suppresses phagocytic activity, as well as lipopolysaccharide (LPS)- stimulated cytokine production in macrophages.
Indirect
Indirect
Indirect
PMID: 18336664, 9756487
One working model for the progression of alcoholic liver disease proposes that increased exposure of Kupffer cells to LPS during chronic ethanol consumption contributes to increased production of inflammatory mediators, in particular tumor necrosis factor TNF-alpha and ROS, leading to the progression of fatty liver, inflammation and fibrosis.
PMID: 18336664, 1940369, 1940799, 8386517
IL-10 then acts to limit excessive production of pro-inflammatory cytokines, including TNF-alpha and IL-1b by decreasing cytokine gene transcription, as well as regulating the stability and/or translation of target mRNAs.
PMID: 18336664
Increased IL-10 expression was ultimately required for the suppression of TLR4-mediated signaling by gAcrp.
Indirect
PMID: 18336664, 12840063
Importantly, treatment of mice with adiponectin during chronic ethanol exposure prevents the development of ethanol-induced liver injury,26 in part by increasing fatty acid oxidation in the liver, thus preventing ethanol-induced steatosis, as well as decreasing TNF-alpha expression.
Indirect
PMID: 18336664, 12840063
Importantly, treatment of mice with adiponectin during chronic ethanol exposure prevents the development of ethanol-induced liver injury,26 in part by increasing fatty acid oxidation in the liver, thus preventing ethanol-induced steatosis, as well as decreasing TNF-alpha expression.
PMID: 18336664, 16410364
Importantly, overnight treatment of Kupffer cells with adiponectin can normalize the chronic ethanol-induced sensitization of LPS-stimulated TNF-alpha expression, normalizing the increased production of ROS, as well as ERK1/2 and p38 phosphorylation.
Indirect
Indirect
PMID: 18336664, 16410364, 15033490, 16325814
In particular, LPS-stimulated NK-kappaB and ERK1/2 activation are sensitive to the inhibitory effects of adiponectin.
Indirect
Indirect
PMID: 18336664, 16410364
Importantly, overnight treatment of Kupffer cells with adiponectin can normalize the chronic ethanol-induced sensitization of LPS-stimulated TNF-alpha expression, normalizing the increased production of ROS, as well as ERK1/2 and p38 phosphorylation.
Indirect
Indirect
PMID: 18336664, 16410364, 15033490, 16325814
In particular, LPS-stimulated NK-kappaB and ERK1/2 activation are sensitive to the inhibitory effects of adiponectin.
PMID: 18336664, 16410364
Importantly, overnight treatment of Kupffer cells with adiponectin can normalize the chronic ethanol-induced sensitization of LPS-stimulated TNF-alpha expression, normalizing the increased production of ROS, as well as ERK1/2 and p38 phosphorylation.
Indirect
PMID: 18336664
IL-10 expression is induced by various inflammatory mediators, such as LPS and TNF-alpha.
Indirect
PMID: 18336664
IL-10 expression is induced by various inflammatory mediators, such as LPS and TNF-alpha.
PMID: 18336664, 17537727
Interestingly, we found that initially adiponectin increases the production of TNF-alpha by RAW 264.7 macrophages; this TNF-alpha, in the continued presence of adiponectin, then increases production of IL-10.
Indirect
Indirect
PMID: 18336664, 1940369, 1940799, 8386517
IL-10 then acts to limit excessive production of pro-inflammatory cytokines, including TNF-alpha and IL-1b by decreasing cytokine gene transcription, as well as regulating the stability and/or translation of target mRNAs.
PMID: 18336664, 17537727
Treatment of RAW 264.7 macrophages with adiponectin increases the expression of IL-10 mRNA and peptide.
PMID: 18336664, 17537727
Interestingly, we found that initially adiponectin increases the production of TNF-alpha by RAW 264.7 macrophages; this TNF-alpha, in the continued presence of adiponectin, then increases production of IL-10.
Indirect
PMID: 18336664, 1940369, 1940799, 8386517
IL-10 then acts to limit excessive production of pro-inflammatory cytokines, including TNF-alpha and IL-1b by decreasing cytokine gene transcription, as well as regulating the stability and/or translation of target mRNAs.
Indirect
PMID: 18336664, 15369797, 17537727
While the mechanisms for the long-term anti-inflammatory effects of adiponectin are not well understood, recent data suggest that adiponectin acts, at least in part, to increase the expression of anti-inflammatory mediators, such as interleukin (IL)-10.
PMID: 18336664, 17537727
Treatment of RAW 264.7 macrophages with adiponectin increases the expression of IL-10 mRNA and peptide.
Indirect
Indirect
PMID: 18336664, 17537727
Interestingly, we found that initially adiponectin increases the production of TNF-alpha by RAW 264.7 macrophages; this TNF-alpha, in the continued presence of adiponectin, then increases production of IL-10.
PMID: 18336664
This initial gAcrp-mediated increase in TNF-alpha production by macrophages was mediated via activation of ERK1/2→Egr-1 and nuclear factor (NF)-kappaB-dependent mechanisms.
Indirect
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter.
Indirect
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter.
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter.
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter.
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter.
Indirect
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter.
PMID: 18336664
gAcrp-stimulated IL-10 expression was also dependent on the phosphorylation of cAMP response element-binding protein and the cAMP response element in the IL-10 promoter.
Indirect
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter (Park, et al., unpubl. obs, 2007); and (ii) an NF-kappaB and Egr-1 pathway, leading to increased production of TNF-alpha.
Indirect
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter (Park, et al., unpubl. obs, 2007); and (ii) an NF-kappaB and Egr-1 pathway, leading to increased production of TNF-alpha.
Indirect
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter (Park, et al., unpubl. obs, 2007); and (ii) an NF-kappaB and Egr-1 pathway, leading to increased production of TNF-alpha.
PMID: 18336664
This initial gAcrp-mediated increase in TNF-alpha production by macrophages was mediated via activation of ERK1/2→Egr-1 and nuclear factor (NF)-kappaB-dependent mechanisms.
Indirect
PMID: 18336664
We next identified two parallel signaling pathways required for adiponectin-stimulated IL-10 transcription: (i) an ERK1/2- and protein kinase A (PKA)-dependent increase in cAMP response element-binding protein (CREB) phosphorylation which acted via the CRE in the IL-10 promoter (Park, et al., unpubl. obs, 2007); and (ii) an NF-kappaB and Egr-1 pathway, leading to increased production of TNF-alpha.
PMID: 18336664
This initial gAcrp-mediated increase in TNF-alpha production by macrophages was mediated via activation of ERK1/2→Egr-1 and nuclear factor (NF)-kappaB-dependent mechanisms.