PMID- 15316034
OWN - NLM
STAT- MEDLINE
DCOM- 20041214
LR  - 20181201
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 76
IP  - 5
DP  - 2004 Nov
TI  - Phosphatase inhibition potentiates IL-6 production by mast cells in response to 
      FcepsilonRI-mediated activation: involvement of p38 MAPK.
PG  - 1075-81
AB  - Mast cells are crucial effector cells in the immune response through mediator 
      secretion and release of cytokines. A coordinated balance between protein kinases 
      and phosphatases plays an essential role in the regulation of mast cell mediator 
      secretion. We have previously shown that treatment of mast cells with okadaic 
      acid (OA), a protein phosphatase 2A (PP2A) inhibitor, results in a dose-dependent 
      increase in interleukin (IL)-6 production. We show here for the first time a 
      synergism between OA and immunoglobulin E (IgE)-mediated IL-6 secretion by murine 
      bone marrow-derived mast cells (BMMC). Selective p38 mitogen-activated protein 
      kinase (p38 MAPK) inhibition reduces OA and IgE-mediated IL-6 production. 
      Regulation of p38 MAPK by PP2A was demonstrated, as OA treatment caused a 
      dose-dependent increase in p38 MAPK phosphorylation. Antigen-mediated activation 
      of murine mast cells also resulted in an increase in p38 MAPK phosphorylation, 
      which was potentiated by cotreatment of the cells with OA. Lastly, in two mast 
      cell lines (human mast cell-1 5C6 and murine MC/9) and primary-cultured murine 
      BMMC, we show by coimmunoprecipitation an interaction between p38 MAPK and PP2A. 
      These data support a role for PP2A through interaction with p38 MAPK in the 
      regulation of IgE-dependent mast cell activation.
FAU - Boudreau, Robert T M
AU  - Boudreau RT
AD  - Department of Microbiology, Dalhousie University, Halifax, Nova Scotia, Canada.
FAU - Hoskin, David W
AU  - Hoskin DW
FAU - Lin, Tong-Jun
AU  - Lin TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040817
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, IgE)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemotaxis, Leukocyte/drug effects/immunology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Immunoglobulin E/*immunology
MH  - Interleukin-6/*biosynthesis/metabolism
MH  - MAP Kinase Signaling System/drug effects/immunology
MH  - Mast Cells/drug effects/immunology/*metabolism
MH  - Mice
MH  - Models, Biological
MH  - Okadaic Acid/pharmacology
MH  - Phosphoprotein Phosphatases/antagonists & inhibitors/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Phosphatase 2
MH  - Receptors, IgE/drug effects/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/drug effects/*metabolism
EDAT- 2004/08/19 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/08/19 05:00
PHST- 2004/08/19 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/08/19 05:00 [entrez]
AID - jlb.1003498 [pii]
AID - 10.1189/jlb.1003498 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2004 Nov;76(5):1075-81. doi: 10.1189/jlb.1003498. Epub 2004 Aug 
      17.