Cleaved fibrinogen products bind TLR4:LY96

Stable Identifier
R-HSA-8870678
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

Fibrinogen, in addition to its role in coagulation, is also an acute phase protein of inflammation which can induce a cytokine production acting as an endogenous ligand for toll-like receptor 4 (TLR4) expressed on cells including macrophages and airway epithelial cells (Millien VO et al., 2013; Kuhns DB et al., 2007; Smiley ST et al., 2001). In human macrophages fibrinogen stimulated interleukin IL6 expression and extracellular signal-related kinase (ERK) phosphorylation ((Hodgkinson CP et al., 2008). In human embryonic kidney 293 (HEK293)-CD14-MD2 cells expressing TLR4, fibrinogen induced robust phosphorylation of ERK1, p38alpha and JNK and activated transcription factors NFkappaB, Elk1 and AP1 (Hodgkinson CP et al., 2008). Moreover, proteinases, such as thrombin, can cleave fibrinogen. In mice, exposure to endogenous or exogenous proteinases lead to hyperactivation of an antifungal pathway and lead to allergic airway inflammation through activation of TLR4-dependent signaling pathway by fibrinogen cleaved products (Millien VO et al., 2013)

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