Open AccessTLR4 Is a Negative Regulator in Noninfectious Lung Inflammation
Author(s) -
Hang Zhao,
ShawWoei Leu,
Liyun Shi,
Rejmon Dedaj,
Gaofeng Zhao,
Hari G. Garg,
Lianjun Shen,
Egil Lien,
Katherine A. Fitzgerald,
Aviva Shiedlin,
Huahao Shen,
Deborah A. Quinn,
Charles A. Hales
Publication year - 2010
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1000009
Subject(s) - tlr4 , inflammation , chemokine , proinflammatory cytokine , immunology , cytokine , in vivo , lung , chemistry , biology , medicine , microbiology and biotechnology
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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