PMID- 7575485
OWN - NLM
STAT- MEDLINE
DCOM- 19951109
LR  - 20201209
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 311 ( Pt 1)
IP  - Pt 1
DP  - 1995 Oct 1
TI  - The protein phosphatase inhibitor calyculin A stimulates chemokine production by 
      human synovial cells.
PG  - 89-95
AB  - Cultured human synovial fibroblasts express mRNA for the chemotactic cytokines 
      (chemokines) interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and 
      regulated upon activation normal T-cell expressed and presumably secreted 
      (RANTES), when stimulated with IL-1 or tumour necrosis factor alpha (TNF alpha). 
      Calyculin A, a potent type 1/2A protein serine/threonine phosphatase inhibitor, 
      was used to examine the role of protein phosphatases in the regulation of 
      chemokine gene expression. Calyculin A (1 nM) mimicked IL-1 by inducing IL-8 and 
      MCP-1 mRNA expression in synovial cells. IL-8 mRNA was induced over a similar 
      time period (1-6 h) in response to IL-1 or calyculin A, whereas MCP-1 mRNA was 
      induced more rapidly (1-2 h) by calyculin A than by IL-1 (4-6 h). Expression of 
      RANTES mRNA occurred in response to TNF alpha, but could not be induced by 
      stimulation with calyculin A alone. These results suggest that inhibition of 
      protein phosphatase type 1/2A may have a differential role in the regulation of 
      the expression of each of the chemokine genes. Synovial fibroblasts also secreted 
      IL-8 and IL-6 peptide when stimulated with either IL-1/TNF alpha or calyculin A. 
      The amount of IL-8 and IL-6 peptide produced in response to calyculin A was 
      significantly increased above that produced by untreated synovial cells, though 
      it was much less than the amount induced by IL-1 or TNF alpha. Calyculin A also 
      acted synergistically with IL-1 or TNF alpha to cause a 2-fold potentiation of 
      IL-1- or TNF alpha-induced IL-8 mRNA and peptide and RANTES mRNA expression. 
      These results suggest that although inhibition of a protein phosphatase may be 
      able to regulate the magnitude of IL-1-induced chemokine gene expression, the 
      IL-1 signal transduction pathway involves components in addition to phosphatase 
      inhibition, possibly including the activation of a protein kinase, the action of 
      which may be opposed by a protein phosphatase inhibited by calyculin A.
FAU - Jordan, N J
AU  - Jordan NJ
AD  - Department of Pharmacology, University of Bath, Claverton Down, U.K.
FAU - Watson, M L
AU  - Watson ML
FAU - Westwick, J
AU  - Westwick J
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ethers, Cyclic)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Marine Toxins)
RN  - 0 (Oxazoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - 7D07U14TK3 (calyculin A)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Chemokine CCL5/biosynthesis
MH  - Cytokines/*biosynthesis
MH  - Enzyme Inhibitors/*pharmacology
MH  - Ethers, Cyclic/pharmacology
MH  - Fibroblasts/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - Interleukin-6/biosynthesis
MH  - Interleukin-8/biosynthesis/genetics
MH  - Marine Toxins
MH  - Okadaic Acid
MH  - Oxazoles/*pharmacology
MH  - Phosphoprotein Phosphatases/*antagonists & inhibitors
MH  - RNA, Messenger/metabolism
MH  - Synovial Membrane/*cytology
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC1136123
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
PMCR- 1995/10/01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
PHST- 1995/10/01 00:00 [pmc-release]
AID - 10.1042/bj3110089 [doi]
PST - ppublish
SO  - Biochem J. 1995 Oct 1;311 ( Pt 1)(Pt 1):89-95. doi: 10.1042/bj3110089.