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Involvement of PKCδ in SP‐induced chemokine production in pancreatic acinar cells
Author(s) -
Ramnath Raina,
Sun Jia,
Adhikari Sharmila,
Bhatia Madhav
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1072.14
Subject(s) - rottlerin , protein kinase c , chemokine , chemistry , microbiology and biotechnology , mapk/erk pathway , kinase , cancer research , medicine , biology , receptor , biochemistry
Pancreatic acinar cells are known to synthesise chemokines, which play critical roles in acute pancreatitis. We have previously investigated the ability of substance P (SP) to produce chemokines MCP‐1, MIP‐1α and MIP‐2 in pancreatic acinar cells, however the exact mechanism by which SP stimulates the synthesis of these pro‐inflammatory mediators remain undetermined. The aim of the current study is to look into the participation of protein kinase C (PKC) in SP‐induced chemokine production in an in vitro model of isolated pancreatic acinar cells. Our results show that SP, interacting with neurokinin 1 receptor (NKIR), stimulated phosphorylation of the PKC isoform PKCδ in pancreatic acinar cells. This was followed by an increased activation in MAPKK kinase MEKK1, MAP kinases ERK and JNK as well as transcription factors, NFκB and AP‐1, driven chemokine production. Inhibition of PKCδ with the specific PKCδ inhibitor rottlerin, dose dependently decreased SP‐ NK1R induced PKCδ, MEKK1, ERK, JNK, NFκB and AP‐1 activation. Moreover, rottlerin significantly inhibited SP‐NK1R induced secretion of MCP‐1, MIP‐1α, and MIP‐2 in a concentration dependent manner in pancreatic acinar cells. The present study demonstrates the role of PKCδ in SP‐induced chemokine production in pancreatic acinar cells and hence PKCδ may be critically involved in the pathogenesis of acute pancreatitis.