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 Blose, David A. Vorp, Heth R. Turnquist, Timothy R. Billiar, Bruce A. Pitt, Ma Zhong Zhang, Li Ming Zhang

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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 1 2017

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HMGB1 Protein
interleukins
epithelial cells
Epithelial Cells
mice
respiratory mucosa
Respiratory Mucosa
Interleukin-33
Maximum likelihood estimation
Biosynthesis
Conditioned Culture Medium
Neutralizing Antibodies
neutralizing antibodies
cytokines
epithelium
Epithelium
biosynthesis
Cytokines
receptors
synthesis

All Science Journal Classification (ASJC) codes

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

Cite this

Chang, Jing ; Xia, Yuefeng ; Wasserloos, Karla ; Deng, Meihong ; Blose, Kory ; Vorp, David A. ; Turnquist, Heth R. ; Billiar, Timothy R. ; Pitt, Bruce A. ; Zhang, Ma Zhong ; Zhang, Li Ming. / Cyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells. In: PloS one. 2017 ; Vol. 12, No. 9.
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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.",
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Chang, J, Xia, Y, Wasserloos, K, Deng, M, Blose, K, Vorp, DA, Turnquist, HR, Billiar, TR, Pitt, BA, Zhang, MZ & Zhang, LM 2017, 'Cyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells', PloS one, vol. 12, no. 9, e0184770. https://doi.org/10.1371/journal.pone.0184770

Cyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells. / Chang, Jing; Xia, Yuefeng; Wasserloos, Karla; Deng, Meihong; Blose, Kory; Vorp, David A.; Turnquist, Heth R.; Billiar, Timothy R.; Pitt, Bruce A.; Zhang, Ma Zhong; Zhang, Li Ming.

In: PloS one, Vol. 12, No. 9, e0184770, 01.09.2017.

Research output: Contribution to journalArticle

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AU - Chang, Jing

AU - Xia, Yuefeng

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AU - Deng, Meihong

AU - Blose, Kory

AU - Vorp, David A.

AU - Turnquist, Heth R.

AU - Billiar, Timothy R.

AU - Pitt, Bruce A.

AU - Zhang, Ma Zhong

AU - Zhang, Li Ming

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N2 - 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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