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Int. J. Biochem. Cell Biol. · Jan 2008
SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by regulating JAK2/STAT3 signaling in pancreas.
- Ji Hoon Yu, Kyung Hwan Kim, and Hyeyoung Kim.
- Department of Pharmacology, College of Medicine, Institute of Gastroenterology, Yonsei University, Seoul 120-752, Republic of Korea.
- Int. J. Biochem. Cell Biol. 2008 Jan 1; 40 (4): 677-88.
AbstractInduction of proinflammatory cytokines IL-6 and TGF-beta1 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-1beta 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-beta1, 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-gamma (PPAR-gamma) ligands, 15d-PGJ2 and troglitazone, induced SOCS 3 expression and inhibited JAK2/STAT3 activation. This treatment regimen also inhibited IL-6 and TGF-beta1 induction, vacuolization, and alpha-smooth muscle actin (alpha-SMA) expression. Thus, SOCS 3 expression is associated with a reduction in IL-6 and TGF-beta1 expression, edema formation, vacuolization, and alpha-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.
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