PMID:17132099 IaI family members are captured on the cell surface through covalent interactions between their heavy chains and hyaluronan bound to CD44, a cell-surface receptor for hyaluronan

PMID: 17132099, 10801881 Two types of bikunin-binding proteins are expressed on the surface of some cells: a 40-kDa protein, which is identical to Link protein, a hyaluronan-binding protein (Kobayashi et al., 2000); and a 45-kDa, as yet unidentified bikunin receptor.

PMID: 17132099 Two types of bikunin-binding proteins are expressed on the surface of some cells: a 40-kDa protein, which is identical to Link protein, a hyaluronan-binding protein (Kobayashi et al., 2000); and a 45-kDa, as yet unidentified bikunin receptor.

PMID: 17132099, 15840581 More recent data demonstrated that bikunin interacts with the Link module of TSG6 (Rugg et al., 2005), cathepsin B (Liu et al., 2006), or the 41-aa C-terminal region of the hepatitis E virus ORF3 protein (Tyagi et al., 2005)

PMID: 17132099, 16364318 More recent data demonstrated that bikunin interacts with the Link module of TSG6 (Rugg et al., 2005), cathepsin B (Liu et al., 2006), or the 41-aa C-terminal region of the hepatitis E virus ORF3 protein (Tyagi et al., 2005)

PMID: 17132099, 16140784 More recent data demonstrated that bikunin interacts with the Link module of TSG6 (Rugg et al., 2005), cathepsin B (Liu et al., 2006), or the 41-aa C-terminal region of the hepatitis E virus ORF3 protein (Tyagi et al., 2005

PMID: 17132099 In particular, TLR4 is part of a recognition complex for LPS.

PMID: 17132099, 11264657, 9916965, 12496270 bikunin inhibits the LPS-induced increase in calcium influx (Onai and Kudo, 2001), which triggers a signal that inactivates mitogen- activated protein kinase kinase wMAPKK (MEK)x/ ERK1/2 and NF-kB, leading to suppression of LPS-induced cytokine synthesis (Futamura et al., 1999; Kobayashi et al., 2003);

PMID: 17132099, 11264657, 9916965, 12496270 bikunin inhibits the LPS-induced increase in calcium influx (Onai and Kudo, 2001), which triggers a signal that inactivates mitogen- activated protein kinase kinase wMAPKK (MEK)x/ ERK1/2 and NF-kB, leading to suppression of LPS-induced cytokine synthesis (Futamura et al., 1999; Kobayashi et al., 2003);

PMID: 17132099, 11264657, 9916965, 12496270 bikunin inhibits the LPS-induced increase in calcium influx (Onai and Kudo, 2001), which triggers a signal that inactivates mitogen- activated protein kinase kinase wMAPKK (MEK)x/ ERK1/2 and NF-kB, leading to suppression of LPS-induced cytokine synthesis (Futamura et al., 1999; Kobayashi et al., 2003);

PMID: 17132099, 11264657 bikunin first directly interacts with bacterial toxins including LPS, which enhances trapping of bacterial toxins (Onai and Kudo, 2001);

PMID:17132099 IaI family members are captured on the cell surface through covalent interactions between their heavy chains and hyaluronan bound to CD44, a cell-surface receptor for hyaluronan

PMID: 17132099, 10801881 bikunin interacts with activated inflammatory cell surfaces via CD44-bound Link protein and/or unknown components, and inactivates some membrane-bound proteinases (Kobayashi et al., 2000);

PMID: 17132099, 10801881 bikunin interacts with activated inflammatory cell surfaces via CD44-bound Link protein and/or unknown components, and inactivates some membrane-bound proteinases (Kobayashi et al., 2000);

PMID: 17132099, 15539418 ERK1/2 also phosphorylates specific nuclear transcription factors PMID: 17132099 Bikunin inhibits LPS-induced ERK1/2 activation by suppressing an increase in calcium influx, leading to suppression of ERK1/2-induced activation of transcription factors, including Egr-1.

PMID: 17132099, 15539418 ERK1/2 also phosphorylates specific nuclear transcription factors PMID: 17132099 Bikunin inhibits LPS-induced ERK1/2 activation by suppressing an increase in calcium influx, leading to suppression of ERK1/2-induced activation of transcription factors, including Egr-1.

PMID: 17132099, 15539418 ERK1/2 also phosphorylates specific nuclear transcription factors PMID: 17132099 Bikunin inhibits LPS-induced ERK1/2 activation by suppressing an increase in calcium influx, leading to suppression of ERK1/2-induced activation of transcription factors, including Egr-1.

PMID: 17132099, 15539418 ERK1/2 also phosphorylates specific nuclear transcription factors PMID: 17132099 Bikunin inhibits LPS-induced ERK1/2 activation by suppressing an increase in calcium influx, leading to suppression of ERK1/2-induced activation of transcription factors, including Egr-1.

PMID: 17132099, 11264657, 9916965, 12496270 bikunin inhibits the LPS-induced increase in calcium influx (Onai and Kudo, 2001), which triggers a signal that inactivates mitogen- activated protein kinase kinase wMAPKK (MEK)x/ ERK1/2 and NF-kB, leading to suppression of LPS-induced cytokine synthesis (Futamura et al., 1999; Kobayashi et al., 2003);

PMID: 17132099, 11264657, 9916965, 12496270 bikunin inhibits the LPS-induced increase in calcium influx (Onai and Kudo, 2001), which triggers a signal that inactivates mitogen- activated protein kinase kinase wMAPKK (MEK)x/ ERK1/2 and NF-kB, leading to suppression of LPS-induced cytokine synthesis (Futamura et al., 1999; Kobayashi et al., 2003);

PMID: 17132099 Cytokine expression can be induced by transcription factors such as NFkB, activating protein-1 (AP-1) and Egr-1, depending on the cell type and stimulus

PMID: 17132099, 11264657, 9916965, 12496270 bikunin inhibits the LPS-induced increase in calcium influx (Onai and Kudo, 2001), which triggers a signal that inactivates mitogen- activated protein kinase kinase wMAPKK (MEK)x/ ERK1/2 and NF-kB, leading to suppression of LPS-induced cytokine synthesis (Futamura et al., 1999; Kobayashi et al., 2003);

PMID: 17132099 IL-6 binds its cell surface receptor

PMID: 17132009, 15576631, 15539418 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132099 Bikunin inhibits LPS-induced ERK1/2 activation by suppressing an increase in calcium influx, leading to suppression of ERK1/2-induced activation of transcription factors, including Egr-1 PMID: 17132099 Cytokine expression can be induced by transcription factors such as NFkB, activating protein-1 (AP-1) and Egr-1, depending on the cell type and stimulus

PMID: 17132099 All the effects can be explained on the basis that bikunin directly interacts with LPS, inactivates the LPS receptor system, or blocks calcium influx.

PMID: 17132009, 15576631, 15539418 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132009, 15539418, 15576631 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132009, 15576631, 15539418 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132009, 15576631, 15539418 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132009, 15576631, 15539418 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132009, 15576631, 15539418 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132009, 15576631, 15539418 It has previously been demonstrated that bikunin inhibits the enhanced local expression or translation not only of proinflammatory cytokines and chemokines, but also of intercellular cell adhesion molecules (ICAM), inducible nitric oxide synthase (iNOS) (Inoue et al., 2005), and tissue factor (Molor-Erdene et al., 2005b).

PMID: 17132099, 7684902 Daveau et al. (1993) reported that IL-6 down-regulated levels of H2 and AMBP mRNA and up-regulated levels of H3 mRNA