Open AccessCyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells
Author(s) -
Jing Chang,
Yuefeng Xia,
Karla Wasserloos,
Meihong Deng,
Kory J. Blose,
David A. Vorp,
Hēth Turnquist,
Timothy R. Billiar,
Bruce R. Pitt,
Ma Zhong Zhang,
Liming Zhang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0184770
Subject(s) - tlr4 , hmgb1 , microbiology and biotechnology , innate immune system , cytokine , signal transduction , receptor , respiratory epithelium , biology , immune system , interleukin , respiratory system , immunology , interleukin 8 , chemistry , inflammation , biochemistry , anatomy
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.