Cyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells.

Autor: Jing Chang, Yuefeng Xia, Karla Wasserloos, Meihong Deng, Kory J Blose, David A Vorp, Heth R Turnquist, Timothy R Billiar, Bruce A Pitt, Ma-Zhong Zhang, Li-Ming Zhang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PLoS ONE, Vol 12, Iss 9, p e0184770 (2017)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0184770
Popis: Interleukin 33 (IL-33), an inflammatory and mechanically responsive cytokine, is an important component of a TLR4-dependent innate immune process in mucosal epithelium. Although TLR4 also plays a role in sensing biomechanical stretch, a pathway of stretch-induced TLR4-dependent IL-33 biosynthesis has not been revealed. In the current study, we show that short term (6 h) cyclic stretch (CS) of cultured murine respiratory epithelial cells (MLE-12) increased intracellular IL-33 expression in a TLR4 dependent fashion. There was no detectable IL-33 in conditioned media in this interval. CS, however, increased release of the notable alarmin, HMGB1, and a neutralizing antibody (2G7) to HMGB1 completely abolished the CS mediated increase in IL-33. rHMGB1 increased IL-33 synthesis and this was partially abrogated by silencing TLR4 suggesting additional receptors for HMGB1 are involved in its regulation of IL-33. Collectively, these data reveal a HMGB1/TLR4/IL-33 pathway in the response of respiratory epithelium to mechanical stretch.
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