Open AccessEffect of mitogen‐activated protein kinases on chemokine synthesis induced by substance P in mouse pancreatic acinar cells
Author(s) -
Ramnath Raina Devi,
Sun Jia,
Adhikari Sharmila,
Bhatia Madhav
Publication year - 2007
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2007.00086.x
Subject(s) - chemokine , mapk/erk pathway , kinase , chemistry , protein kinase a , microbiology and biotechnology , signal transduction , mitogen activated protein kinase , biology , receptor , biochemistry
Substance P, acting via its neurokinin 1 receptor (NK1 R), plays an important role in mediating a variety of inflammatory processes. Its interaction with chemokines is known to play a crucial role in the pathogenesis of acute pancreatitis. In pancreatic acinar cells, substance P stimulates the release of NFκB‐driven chemokines. However, the signal transduction pathways by which substance P‐NK1 R interaction induces chemokine production are still unclear. To that end, we went on to examine the participation of mitogen‐activated protein kinases (MAPKs) in substance P‐induced synthesis of pro‐inflammatory chemokines, monocyte chemoanractant protein‐1 (MCP‐I), macrophage inflammatory protein‐lα (MIP‐lα) and macrophage inflammatory protein‐2 (MIP‐2), in pancreatic acini. In this study, we observed a time‐dependent activation of ERK1/2, c‐Jun N‐terminal kinase (JNK), NFκB and activator protein‐1 (AP‐1) when pancreatic acini were stimulated with substance P. Moreover, substance P‐induced ERK 1/2, JNK, NFκB and AP‐1 activation as well as chemokine synthesis were blocked by pre‐treatment with either extracellular signal‐regulated protein kinase kinase 1 (MEK1) inhibitor or JNK inhibitor. In addition, substance P‐induced activation of ERK 112, JNK, NFκB and AP‐1‐driven chemokine production were attenuated by CP96345, a selective NK1 R antagonist, in pancreatic acinar cells. Taken together, these results suggest that substance P‐NK1 R induced chemokine production depends on the activation of MAPKs‐mediated NFκB and AP‐1 signalling pathways in mouse pancreatic acini.