Pancreatitis-Associated Protein I Suppresses NF-kappaB Activation through a JAK/STAT-Mediated Mechanism in Epithelial Cells Export

@article{Folch-Puy2006, abstract = {Pancreatitis-associated protein I (PAP I), also known as HIP, p23, or Reg2 protein, has recently been implicated in the endogenous regulation of inflammation. Although it was initially characterized as a protein that is overexpressed in acute pancreatitis, PAP I has also been associated with a number of inflammatory diseases, such as Crohn's disease. Knowing that PAP I and IL-10 responses share several features, we have used a pancreatic acinar cell line (AR42J) to assess the extent to which their expression is reciprocally regulated, and whether the JAK/STAT and NF-kappaB signaling pathways are involved in the suppression of inflammation mediated by PAP I. We observed that PAP I is induced in epithelial cells by IL-10 and by PAP I itself. In contrast, we found phosphorylation and nuclear translocation of STAT3 and induction of suppressor of cytokine signaling 3 in response to PAP I exposure. Finally, a JAK-specific inhibitor, tyrphostin AG490, markedly prevented PAP I-induced NF-kappaB inhibition, pointing to a cross-talk between JAK/STAT3 and NF-kappaB signaling pathways. Together, these findings indicate that PAP I inhibits the inflammatory response by blocking NF-kappaB activation through a STAT3-dependent mechanism. Important functional similarities to the anti-inflammatory cytokine IL-10 suggest that PAP I could play a role similar to that of IL-10 in epithelial cells.}, author = {Folch-Puy, Emma and Granell, Susana and Dagorn, Jean C. and Iovanna, Juan L. and Closa, Daniel}, citeulike-article-id = {789667}, citeulike-linkout-0 = {http://www.jimmunol.org/cgi/content/abstract/176/6/3774}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16517747}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16517747}, day = {15}, journal = {J Immunol}, keywords = {epithelial, nfkb, pap1}, month = {March}, number = {6}, pages = {3774--3779}, posted-at = {2006-08-08 09:10:16}, priority = {2}, title = {Pancreatitis-Associated Protein I Suppresses NF-kappaB Activation through a JAK/STAT-Mediated Mechanism in Epithelial Cells}, url = {http://www.jimmunol.org/cgi/content/abstract/176/6/3774}, volume = {176}, year = {2006} }

TY - JOUR ID - Folch-Puy2006 L3 - citeulike-article-id:789667 N2 - Pancreatitis-associated protein I (PAP I), also known as HIP, p23, or Reg2 protein, has recently been implicated in the endogenous regulation of inflammation. Although it was initially characterized as a protein that is overexpressed in acute pancreatitis, PAP I has also been associated with a number of inflammatory diseases, such as Crohn's disease. Knowing that PAP I and IL-10 responses share several features, we have used a pancreatic acinar cell line (AR42J) to assess the extent to which their expression is reciprocally regulated, and whether the JAK/STAT and NF-kappaB signaling pathways are involved in the suppression of inflammation mediated by PAP I. We observed that PAP I is induced in epithelial cells by IL-10 and by PAP I itself. In contrast, we found phosphorylation and nuclear translocation of STAT3 and induction of suppressor of cytokine signaling 3 in response to PAP I exposure. Finally, a JAK-specific inhibitor, tyrphostin AG490, markedly prevented PAP I-induced NF-kappaB inhibition, pointing to a cross-talk between JAK/STAT3 and NF-kappaB signaling pathways. Together, these findings indicate that PAP I inhibits the inflammatory response by blocking NF-kappaB activation through a STAT3-dependent mechanism. Important functional similarities to the anti-inflammatory cytokine IL-10 suggest that PAP I could play a role similar to that of IL-10 in epithelial cells. IS - 6 JF - J Immunol EP - 3779 TI - Pancreatitis-Associated Protein I Suppresses NF-kappaB Activation through a JAK/STAT-Mediated Mechanism in Epithelial Cells VL - 176 SP - 3774 KW - epithelial KW - nfkb KW - pap1 AU - Folch-Puy, Emma AU - Granell, Susana AU - Dagorn, Jean AU - Iovanna, Juan AU - Closa, Daniel PY - 2006/03/15/ UR - http://www.jimmunol.org/cgi/content/abstract/176/6/3774 ER -