Gene interactions and pathways from curated databases and text-mining
Am J Physiol Gastrointest Liver Physiol 2008, PMID: 18239058

Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-32alpha induction in human pancreatic periacinar myofibroblasts.

Nishida, Atsushi; Andoh, Akira; Shioya, Makoto; Kim-Mitsuyama, Shokei; Takayanagi, Atsushi; Fujiyama, Yoshihide

Interleukin (IL)-32 is a recently described proinflammatory cytokine, characterized by the induction of nuclear factor (NF)-kappaB activation. We studied IL-32alpha expression in human pancreatic periacinar myofibroblasts, which play important roles in the regulation of extracellular matrix metabolism and inflammatory responses in the pancreas. IL-32alpha protein expression was evaluated by Western blot analyses, and IL-32alpha mRNA expression was analyzed by Northern blot and real-time PCR analyses. IL-32alpha mRNA was weakly expressed without a stimulus, and its expression was markedly enhanced by IL-1beta, IFN-gamma, and TNF-alpha. IL-1beta, IFN-gamma, and TNF-alpha enhanced intracellular accumulation of IL-32alpha protein, but IL-32alpha was not detected in supernatants. Each cytokine dose and time dependently induced IL-32alpha mRNA expression. An inhibitor of phosphatidylinositol 3-kinase (LY294002) significantly suppressed IL-1beta-, IFN-gamma-, and TNF-alpha-induced IL-32alpha mRNA expression, although MAPK inhibitors had no effect. Akt activation in response to these cytokines was confirmed by Western blot. Furthermore, LY294002 suppressed both IL-1beta- and TNF-alpha-induced NF-kappaB activation and IL-1beta-, TNF-alpha-, and IFN-gamma-induced activated protein-1 (AP-1) activation. Blockade of NF-kappaB and AP-1 activation by an adenovirus expressing a stable mutant form of IkappaBalpha and a dominant negative mutant of c-Jun markedly suppressed IL-1beta-, IFN-gamma-, and/or TNF-alpha-induced IL-32alpha mRNA expression. Human pancreatic periacinar myofibroblasts expressed IL-32alpha in response to IL-1beta, TNF-alpha, and IFN-gamma. IL-32alpha mRNA expression is dependent on interactions between the phosphatidylinositol 3-kinase/Akt-pathway and the NF-kappaB/AP-1 system.

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Text Mining Data

interleukin-32alpha → 3-kinase/Akt: " Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-32alpha induction in human pancreatic periacinar myofibroblasts "

interleukin-32alpha → Phosphatidylinositol 3-kinase/Akt: " Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-32alpha induction in human pancreatic periacinar myofibroblasts "

IL-32alpha → TNF-alpha: " IL-1beta, IFN-gamma, and TNF-alpha enhanced intracellular accumulation of IL-32alpha protein, but IL-32alpha was not detected in supernatants "

IL-32alpha → IFN-gamma: " IL-1beta, IFN-gamma , and TNF-alpha enhanced intracellular accumulation of IL-32alpha protein, but IL-32alpha was not detected in supernatants "

IL-32alpha → IL-1beta: " IL-1beta , IFN-gamma, and TNF-alpha enhanced intracellular accumulation of IL-32alpha protein, but IL-32alpha was not detected in supernatants "

IL-32alpha → TNF-alpha: " An inhibitor of phosphatidylinositol 3-kinase ( LY294002 ) significantly suppressed IL-1beta-, IFN-gamma-, and TNF-alpha induced IL-32alpha mRNA expression, although MAPK inhibitors had no effect "

TNF-alpha- → TNF-alpha: " Furthermore, LY294002 suppressed both IL-1beta- and TNF-alpha induced NF-kappaB activation and IL-1beta-, TNF-alpha- , and IFN-gamma induced activated protein-1 (AP-1) activation "

activated protein-1 (AP-1) → TNF-alpha: " Furthermore, LY294002 suppressed both IL-1beta- and TNF-alpha induced NF-kappaB activation and IL-1beta-, TNF-alpha-, and IFN-gamma induced activated protein-1 (AP-1) activation "

activated protein-1 (AP-1) → IFN-gamma: " Furthermore, LY294002 suppressed both IL-1beta- and TNF-alpha induced NF-kappaB activation and IL-1beta-, TNF-alpha-, and IFN-gamma induced activated protein-1 (AP-1) activation "

IL-1beta- → TNF-alpha: " Furthermore, LY294002 suppressed both IL-1beta- and TNF-alpha induced NF-kappaB activation and IL-1beta- , TNF-alpha-, and IFN-gamma induced activated protein-1 (AP-1) activation "

NF-kappaB → TNF-alpha: " Furthermore, LY294002 suppressed both IL-1beta- and TNF-alpha induced NF-kappaB activation and IL-1beta-, TNF-alpha-, and IFN-gamma induced activated protein-1 (AP-1) activation "

IL-32alpha → TNF-alpha: " Blockade of NF-kappaB and AP-1 activation by an adenovirus expressing a stable mutant form of IkappaBalpha and a dominant negative mutant of c-Jun markedly suppressed IL-1beta-, IFN-gamma-, and/or TNF-alpha induced IL-32alpha mRNA expression "

IL-32alpha → TNF-alpha: " Human pancreatic periacinar myofibroblasts expressed IL-32alpha in response to IL-1beta, TNF-alpha , and IFN-gamma "

IL-32alpha → IFN-gamma: " Human pancreatic periacinar myofibroblasts expressed IL-32alpha in response to IL-1beta, TNF-alpha, and IFN-gamma "

IL-32alpha → IL-1beta: " Human pancreatic periacinar myofibroblasts expressed IL-32alpha in response to IL-1beta , TNF-alpha, and IFN-gamma "

IL-32alpha → 3-kinase/Akt-pathway: " IL-32alpha mRNA expression is dependent on interactions between the phosphatidylinositol 3-kinase/Akt-pathway and the NF-kappaB/AP-1 system "

Manually curated Databases

No curated data.