JAK and STAT proteins are expressed and activated by IFN-gamma in rat pancreatic acinar cells.

The development of acute pancreatitis (AP) is triggered by acinar events, but the subsequent extra-acinar events, particularly a distinct immune response, appear to determine its severity. Cytokines modulate this immune response and are derived not only from immunocytes but also from pancreatic acinar cells. We studied whether pancreatic acinar cells were also capable of responding to cytokines. The JAK/STAT-pathway represents the main effector for many cytokines. Therefore, expression and regulation of JAK and STAT proteins were investigated in rat pancreatic acinar cells. Western blotting showed expression of JAK1, JAK2, Tyk2, and STAT1, STAT2, STAT3, STAT5, STAT6. In addition, STAT1 was reversibly tyrosine-phosphorylated upon the procedure of acinar cell isolation. In contrast, STAT3-phosphorylation occurred spontaneously after pancreas removal and was not reversible within 8 h. STAT1 phosphorylation was also observed upon treatment with IFN-gamma but not upon EGF, TNF-alpha or IL-6, and inhibited by the JAK2-inhibitor AG-490. Immunohistochemistry revealed cytoplasmic expression of unphosphorylated STAT1 in untreated acinar cells and nuclear translocation of phosphorylated STAT1 following IFN-gamma-treatment. Interestingly, although CCK leads to the activation of multiple stress pathways in pancreatic acinar cells, we found no influence of CCK on phosphorylation of STAT1, STAT3, or STAT5 in the pancreas. In conclusion, our data provide further evidence that pancreatic acinar cells are able to interact with immune cells. Besides stimulating immune cells via cytokine secretion, acinar cells are in turn capable of responding to IFN-gamma via JAK2 and STAT1 which may have an impact on the development of AP.

Gallmeier E ，Schäfer C ，Moubarak P ，Tietz A ，Plössl I ，Huss R ，Göke B ，Wagner AC ... -  《JOURNAL OF CELLULAR PHYSIOLOGY》

Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells.

Huang JS ，Guh JY ，Hung WC ，Yang ML ，Lai YH ，Chen HC ，Chuang LY ... -  《-》

AG490 prevents cell death after exposure of rat astrocytes to hydrogen peroxide or proinflammatory cytokines: involvement of the Jak2/STAT pathway.

Gorina R ，Petegnief V ，Chamorro A ，Planas AM ... -  《JOURNAL OF NEUROCHEMISTRY》

Differential requirements for JAK2 and TYK2 in T cell proliferation and IFN-gamma production induced by IL-12 alone or together with IL-18.

Sugimoto N ，Nakahira M ，Ahn HJ ，Micallef M ，Hamaoka T ，Kurimoto M ，Fujiwara H ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》

Type I and type II interferons delay human neutrophil apoptosis via activation of STAT3 and up-regulation of cellular inhibitor of apoptosis 2.

Sakamoto E ，Hato F ，Kato T ，Sakamoto C ，Akahori M ，Hino M ，Kitagawa S ... -  《JOURNAL OF LEUKOCYTE BIOLOGY》