SOCS 3 and PPAR-γ ligands inhibit the expression of IL-6 and TGF-β1 by regulating JAK2/STAT3 signaling in pancreas

Ji Hoon Yu, Kyung Hwan Kim, Hyeyoung Kim

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Induction of proinflammatory cytokines IL-6 and TGF-β1 are the hallmark of human pancreatitis. Cerulein pancreatitis is similar to human edematous pancreatitis involving dysregulation of digestive enzyme production, cytoplasmic vacuolization, and increased cytokine production. We previously showed that cerulein induced IL-1β expression through the Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway in pancreatic acinar cells. Suppressor of cytokine signaling (SOCS) is a negative feedback regulator of JAK/STAT signaling. In this study, we demonstrate that SOCS 3 is induced by cerulein in pancreatic acinar AR42J cells and in the rat pancreas. In both AR42J cells and rat pancreas, cerulein induced expression of IL-6 and TGF-β1, which is enhanced by transfection or injection of SOCS 3 antisense oligonucleotide (AS ODN). Pre-treating cerulein-stimulated AR42J cells or rats with the peroxisome proliferator activated receptor-γ (PPAR-γ) ligands, 15d-PGJ2 and troglitazone, induced SOCS 3 expression and inhibited JAK2/STAT3 activation. This treatment regimen also inhibited IL-6 and TGF-β1 induction, vacuolization, and α-smooth muscle actin (α-SMA) expression. Thus, SOCS 3 expression is associated with a reduction in IL-6 and TGF-β1 expression, edema formation, vacuolization, and α-SMA expression, possibly by direct regulation of JAK2/STAT3 signaling. 15d-PGJ2 and troglitazone are potentially useful pancreatitis therapies by suppressing the JAK2/STAT3 inflammatory signaling through SOCS 3 induction.

Original languageEnglish
Pages (from-to)677-688
Number of pages12
JournalInternational Journal of Biochemistry and Cell Biology
Volume40
Issue number4
DOIs
Publication statusPublished - 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'SOCS 3 and PPAR-γ ligands inhibit the expression of IL-6 and TGF-β1 by regulating JAK2/STAT3 signaling in pancreas'. Together they form a unique fingerprint.

  • Cite this