PMID- 22578382
OWN - NLM
STAT- MEDLINE
DCOM- 20120809
LR  - 20161125
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 52
IP  - 2
DP  - 2012 Sep
TI  - Calcium/calmodulin-dependent protein kinase II regulates IL-10 production by 
      human T lymphocytes: a distinct target in the calcium dependent pathway.
PG  - 51-60
LID - 10.1016/j.molimm.2012.04.008 [doi]
AB  - Calcium (Ca2+) plays an essential role in lymphocyte activation and 
      differentiation by affecting signaling pathways leading to cytokine production. 
      Among the enzymes responding to calcium increase, Ca2+/calmodulin-dependent 
      protein kinase II (CaMKII) has been involved in anergy with a still poorly 
      characterized role. IL-10 produced by different T lymphocyte subpopulations is 
      critical mediator of tolerance. We tested the hypothesis that CaMKII may be 
      involved in IL-10 production. We report that CaMKII upregulates IL-10 production 
      by primary human T lymphocytes stimulated through the antigen receptor or 
      bypassing that. Overexpression of constitutively active mutant forms of 
      Calcineurin or CaMKII specifically increase IL-10 protein product and IL-10 mRNA 
      accumulation in T lymphocytes. By cotransfecting constitutively active CaMKII 
      with luciferase reporter plasmids carrying specific fragments or the whole IL-10 
      promoter, we show that CaMKII specifically activates IL-10 promoter activity, 
      whereas it inhibits IL-2 and IL-4 promoter. This effect is mediated by the first 
      500 bp fragment, which contains binding sites for Myocyte Enhancer Factor-2 
      (MEF2). A constitutively active mutant of CaMKII activated a luciferase reporter 
      plasmid under the control of MEF2, when cotransfected in T lymphocytes stimulated 
      by Ionomycin and PMA, whereas its inhibitor KN-62 inhibited MEF2 binding in cell 
      lysates of the same cells. Moreover, overexpression of MEF2 enhanced by 2.5-fold 
      IL-10 promoter activity. Our data for the first time suggest a distinct role of 
      CaMKII in the induction of anergy in T lymphocytes, by differential regulation of 
      IL-10 and IL-2 gene transcription suggest MEF2 as a molecular target which can 
      integrate different calcium signals.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Boubali, Stavroula
AU  - Boubali S
AD  - Department of Microbiology, School of Medicine, University of Patras, Asclepiou 
      Street, 26500 Patras, Greece.
FAU - Liopeta, Kassiani
AU  - Liopeta K
FAU - Virgilio, Laura
AU  - Virgilio L
FAU - Thyphronitis, George
AU  - Thyphronitis G
FAU - Mavrothalassitis, George
AU  - Mavrothalassitis G
FAU - Dimitracopoulos, George
AU  - Dimitracopoulos G
FAU - Paliogianni, Fotini
AU  - Paliogianni F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120510
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (IL10 protein, human)
RN  - 0 (MADS Domain Proteins)
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (MEF2D protein, human)
RN  - 0 (Myogenic Regulatory Factors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 130068-27-8 (Interleukin-10)
RN  - 63HM46XPOW (KN 62)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 3.1.3.16 (Calcineurin)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology
MH  - Base Sequence
MH  - Calcineurin/metabolism
MH  - Calcineurin Inhibitors
MH  - Calcium Signaling
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & 
      inhibitors/*metabolism
MH  - Cells, Cultured
MH  - Humans
MH  - Interleukin-10/*biosynthesis/genetics
MH  - MADS Domain Proteins/genetics
MH  - MEF2 Transcription Factors
MH  - Myogenic Regulatory Factors/genetics
MH  - Promoter Regions, Genetic
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - T-Lymphocytes/drug effects/*immunology/*metabolism
MH  - Up-Regulation
EDAT- 2012/05/15 06:00
MHDA- 2012/08/10 06:00
CRDT- 2012/05/15 06:00
PHST- 2012/02/07 00:00 [received]
PHST- 2012/04/13 00:00 [accepted]
PHST- 2012/05/15 06:00 [entrez]
PHST- 2012/05/15 06:00 [pubmed]
PHST- 2012/08/10 06:00 [medline]
AID - S0161-5890(12)00250-7 [pii]
AID - 10.1016/j.molimm.2012.04.008 [doi]
PST - ppublish
SO  - Mol Immunol. 2012 Sep;52(2):51-60. doi: 10.1016/j.molimm.2012.04.008. Epub 2012 
      May 10.