PMID- 7750575
OWN - NLM
STAT- MEDLINE
DCOM- 19950622
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 364
IP  - 2
DP  - 1995 May 8
TI  - Pyrrolidine dithiocarbamate differentially affects cytokine- and cAMP-induced 
      expression of group II phospholipase A2 in rat renal mesangial cells.
PG  - 218-22
AB  - Renal mesangial cells express group II phospholipase A2 in response to two 
      principal classes of activating signals that may interact in a synergistic 
      fashion. These two groups of activators comprise inflammatory cytokines such as 
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) 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 NF kappa B, we determined its role in cytokine--and 
      cAMP--triggered group II PLA2 expression. Micromolar amounts of PDTC suppress the 
      IL-1 beta- and TNF alpha-dependent, but not the forskolin-stimulated group II 
      PLA2 activity in mesangial cells. Furthermore, PDTC inhibited the increase of 
      group II PLA2 mRNA steady state levels in response to IL-1 beta and TNF alpha, 
      while only marginally affecting forskolin-induced PLA2 mRNA levels. Our data 
      suggest that NF kappa B activation is an essential component of the cytokine 
      signalling pathway responsible for group II PLA2 gene regulation and that cAMP 
      triggers a separate signalling cascade not involving NF kappa B. These 
      observations may provide a basis to study the underlying mechanisms involved in 
      the regulation of group II PLA2 gene expression.
FAU - Walker, G
AU  - Walker G
AD  - Department of Pharmacology, University of Basel, Switzerland.
FAU - Kunz, D
AU  - Kunz D
FAU - Pignat, W
AU  - Pignat W
FAU - van den Bosch, H
AU  - van den Bosch H
FAU - Pfeilschifter, J
AU  - Pfeilschifter J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Interleukin-1)
RN  - 0 (Pyrrolidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thiocarbamates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1F7A44V6OU (Colforsin)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Glomerular Mesangium/*drug effects/*enzymology
MH  - Interleukin-1/pharmacology
MH  - Phospholipases A/classification/*genetics
MH  - Phospholipases A2
MH  - Pyrrolidines/*pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Thiocarbamates/*pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1995/05/08 00:00
MHDA- 1995/05/08 00:01
CRDT- 1995/05/08 00:00
PHST- 1995/05/08 00:00 [pubmed]
PHST- 1995/05/08 00:01 [medline]
PHST- 1995/05/08 00:00 [entrez]
AID - 0014-5793(95)00402-U [pii]
AID - 10.1016/0014-5793(95)00402-u [doi]
PST - ppublish
SO  - FEBS Lett. 1995 May 8;364(2):218-22. doi: 10.1016/0014-5793(95)00402-u.