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

• Published in: PloS one Vol. 12; no. 9; p. e0184770
• Main Authors: Chang, Jing, Xia, Yuefeng, Wasserloos, Karla, Deng, Meihong, Blose, Kory J, Vorp, David A, Turnquist, Heth R, Billiar, Timothy R, Pitt, Bruce A, Zhang, Ma-Zhong, Zhang, Li-Ming
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.09.2017; Public Library of Science (PLoS)
• Subjects: Allergies; Anesthesiology; Animals; Bioengineering; Biology and life sciences; Biomechanics; Biosynthesis; Cardiomyocytes; Cell Line; Cellular signal transduction; Conditioned stimulus; Conditioning; Cytokines; Epithelial cells; Epithelium; Gene expression; Genetic aspects; HMGB1 protein; HMGB1 Protein - metabolism; Immunology; Inflammation; Interleukin-33 - genetics; Interleukin-33 - metabolism; Interleukins; Ligands; Mechanotransduction, Cellular; Medicine; Medicine and Health Sciences; Mice; Molecular biology; Mucosal immunity; Occupational health; Physiological aspects; Physiology; Public health; Receptors; Research and Analysis Methods; Respiratory Mucosa - metabolism; Respiratory tract; Rodents; Second Messenger Systems; Signal transduction; Stress, Mechanical; Surgery; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; United States; China; United States > US; Pittsburgh Pennsylvania; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184770

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.