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Publication : TLR4 is a negative regulator in noninfectious lung inflammation.

First Author  Zhao H Year  2010
Journal  J Immunol Volume  184
Issue  9 Pages  5308-14
PubMed ID  20357263 Mgi Jnum  J:160454
Mgi Id  MGI:4454483 Doi  10.4049/jimmunol.1000009
Citation  Zhao H, et al. (2010) TLR4 Is a negative regulator in noninfectious lung inflammation. J Immunol 184(9):5308-14
abstractText  Low m.w. hyaluronan (LMW HA) has been shown to elicit the expression of proinflammatory cytokines and chemokines in various cells in vitro. However, the effects of this molecule in vivo are unknown. In this study, we report that intratracheal administration of LMW HA (200 kDa) causes inflammation in mouse lung. A lack of TLR4 is associated with even stronger inflammatory response in the lung as shown by increased neutrophil counts and elevated cytokine and chemokine concentrations. We also demonstrate that TLR4 anti-inflammatory signaling is dependent upon a MyD88-independent pathway. TLR4-mediated IL-1R antagonist production plays a negative regulatory role in LMW HA (200 kDa) induced lung inflammation. These data provide a molecular level explanation for the function of TLR4 in LMW HA (200 kDa)-induced lung inflammation, as inhibition of the beta form of pro-IL-1 promotes an anti-inflammatory response.
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