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Pyrrolidine dithiocarbamate differentially affects cytokine‐ and cAMP‐induced expression of group II phospholipase A 2 in rat renal mesangial cells
Author(s) -
Gaby Walker,
Dieter Kunz,
Werner Pignat,
H. van den Bosch,
Josef Pfeilschifter
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00402-u
Subject(s) - pyrrolidine dithiocarbamate , dithiocarbamate , pyrrolidine , chemistry , cytokine , medicine , endocrinology , phospholipase c , phospholipase a2 , phospholipase a , biochemistry , biology , stereochemistry , enzyme , signal transduction , nf κb , organic chemistry
Renal mesangial cells express group II phospholipase A 2 in response to two principal classes activating signals that may interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNFα) and agents that elevate cellular levels of cAMP such as forskolin, an activator of adenylate cyclase. Using pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of nuclear factor NFκB, we determined its role in cytokine — and cAMP — triggered group II PLA 2 expression. Micromolar amounts of PDTC suppress the IL‐1β‐ and TNF α‐dependent, but not the forskolin‐stimulated group II PLA 2 activity in mesangial cells. Furthermore, PDTC inhibited the increase of group II PLA 2 mRNA steady state levels in response to IL‐1β and TNFα, while only marginally affecting forskolin‐induced PLA 2 mRNA level. Our data suggest that NFκB activation is an essential component of the cytokine signalling pathway responsible for group II PLA 2 gene regulation and that cAMP triggers a separate signalling cascade not involving NFκB. These observations may provide a basis to study the underlying mechanisms involved in the regulation of group II PLA 2 gene expression.