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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere0184770
JournalPloS one
Volume12
Issue number9
DOIs
StatePublished - Sep 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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