Nuclear expression of interleukin-33 in pancreatic stellate cells

Atsushi Masamune, Takashi Watanabe, Kazuhiro Kikuta, Kennichi Satoh, Atsushi Kanno, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

Activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have suggested a role of IL-33, a newly identified IL-1 family member, in fibrosis. We here examined the expression of IL-33 and the IL-33-mediated regulation of cell functions in PSCs. PSCs were isolated from human and rat pancreas tissues. The expression of IL-33 was examined by Western blotting, PCR, ELISA, and immunostaining. The roles of IL-33 in the regulation of PSC functions were examined by using recombinant IL-33 and small interfering RNA. Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1β, TNF-α, PDGF-BB, and IFN-γ, but not TGF-β1. Nuclear IL-33 expression was also observed in the pancreatic acinar and ductal cells. IL-1β induced IL-33 expression mainly through the activation of NF-κB and ERK pathways and partially through that of p38 MAP kinase, whereas PDGF-BB induced IL-33 expression mainly through the activation of ERK pathway. PSCs expressed soluble ST2, ST2L, and IL-1RAcP, but the expression level of ST2L was relatively low. Recombinant IL-33 did not stimulate key cell functions of PSCs. Decreased IL-33 expression by small interfering RNA resulted in decreased proliferation in response to PDGF-BB. In conclusion, activated PSCs expressed IL-33 in the nucleus. IL-33 might regulate the PDGF-induced proliferation in PSCs.

Original languageEnglish
Pages (from-to)G821-G832
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume299
Issue number4
DOIs
Publication statusPublished - 2010 Oct

Keywords

  • Fibrosis
  • Inflammation
  • Pancreatic cancer
  • Pancreatitis
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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