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PLoS One. 2017 Sep 12;12(9):e0184770. doi: 10.1371/journal.pone.0184770. eCollection 2017.

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

Author information

1
Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
2
Department of Environmental and Occupational Health, University of Pittsburgh Graduate School Public Health, Pittsburgh, Pennsylvania, United States of America.
3
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
4
Department of Anesthesiology, Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Hunan, China.
5
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
6
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
7
Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

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.

PMID:
28898270
PMCID:
PMC5595336
DOI:
10.1371/journal.pone.0184770
[Indexed for MEDLINE]
Free PMC Article

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