TLR3 activation evokes IL-6 secretion, autocrine regulation of Stat3 signaling and TLR2 expression in human bronchial epithelial cells.

ABSTRACT: Human bronchial epithelial cells exposed to synthetic double-stranded RNA (poly I:C) exhibited increased IL-6 and RANTES secretion and TLR2 expression that was inhibited following TLR3 silencing. Increased NF-?B and Stat3 phosphorylation were detected after poly I:C exposure and pretreatment with neutralizing antibody targeting IL-6 receptor ? (IL-6R? -nAb) or blocking Jak2 and Stat3 activity inhibited Stat3 phosphorylation. TLR2 up-regulation by poly I:C was also reduced by IL-6R?-nAb and inhibitors of Jak2, Stat3 and NF-?B phosphorylation, whereas RANTES secretion was unaffected, but abolished following NF-?B inhibition. Treatment with exogenous IL-6 failed to increase TLR2. These findings demonstrate that TLR3 activation differentially regulates TLR expression through autocrine signaling involving IL-6 secretion, IL-6R? activation and subsequent phosphorylation of Stat3. The results also indicate that NF-?B and Stat3 are required for TLR3-dependent up-regulation of TLR2 and that its delayed expression was due to a requirement for IL-6-dependent Stat3 activation.

SUBMITTER: Melkamu T 

PROVIDER: S-EPMC3660690 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature