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Publication : Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.

First Author  Millien VO Year  2013
Journal  Science Volume  341
Issue  6147 Pages  792-6
PubMed ID  23950537 Mgi Jnum  J:199356
Mgi Id  MGI:5502460 Doi  10.1126/science.1240342
Citation  Millien VO, et al. (2013) Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4. Science 341(6147):792-6
abstractText  Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are essential for expression of allergic inflammation and diseases such as asthma. A mechanism that links these inflammatory mediators is essential for explaining the fundamental basis of allergic disease but has been elusive. Here, we demonstrate that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages. Thus, allergic airway inflammation represents an antifungal defensive strategy that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify the molecular basis of allergic disease and suggest new therapeutic strategies.
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