PMID- 9301524
OWN - NLM
STAT- MEDLINE
DCOM- 19970930
LR  - 20220227
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 91
IP  - 3
DP  - 1997 Jul
TI  - Differential regulation of IFN-gamma, IL-10 and inducible nitric oxide synthase 
      in human T cells by cyclic AMP-dependent signal transduction pathway.
PG  - 361-8
AB  - Expression of cytokines by T lymphocytes is a highly balanced process, involving 
      stimulatory and inhibitory intracellular signalling pathways. In the present 
      work, we attempted to clarify the role of cAMP on interferon-gamma (IFN-gamma), 
      interleukin (IL)-10, IL-4 and IL-13 expression as well as on the inducible nitric 
      oxide synthase (iNOS) expression. Treatment of phytohaemagglutinin (PHA)/phorbol 
      12-myristate 13-acetate (PMA)-activated Jurkat cells with either dibutyryl-cyclic 
      adenosine monophosphate (cAMP) or pentoxifylline induced a strong inhibition of 
      IFN-gamma mRNA expression as measured by reverse transcription (RT)-polymerase 
      chain reaction (PCR), without affecting IL-10 expression. Both cholera toxin and 
      prostaglandin E2 (PGE2) induced a strong inhibition of IFN-gamma mRNA expression, 
      whereas IL-10 mRNA expression was significantly enhanced. This differential 
      regulation of IFN-gamma and IL-10 expression was related to intracellular cAMP 
      concentration. IL-13 and IL-4 mRNA expressions were not inhibited. We developed a 
      new method based on immunofluorescence for intracellular cytokine detection 
      followed by optical and computerized image processing, and our results showed 
      that IFN-gamma protein was strongly inhibited when cells were treated with PGE2 
      or dibutyryl (db)-cAMP, whereas IL-10 protein was enhanced. This suggests that 
      cAMP exerts its action at both the transcriptional and protein levels. iNOS mRNA 
      expression was markedly elevated in the presence of PGE2. The generation of 
      nitric oxide using sodium nitroprusside (SNP) induced a dramatic decrease of 
      IFN-gamma, while IL-10 was enhanced; and conversely the inhibition of iNOS 
      activity using 1-NG-monomethyl arginine (1-NMMA) induced a clear inhibition of 
      IL-10 and IL-4, while IFN-gamma was enhanced. These results provide evidence that 
      the protein kinase A (PKA) activation pathway plays a prominent role in the 
      balance between the type 1 and type 2 cytokine profile in PHA/PMA-activated 
      Jurkat cells. Data also suggest that iNOS expression is under the control of PKA 
      activation, and that NO seems to be able to assume the polarization of activated 
      T cells to the type 2 profile.
FAU - Benbernou, N
AU  - Benbernou N
AD  - Laboratoire d'Immunologie, Faculte de Pharmacie de Reims, France.
FAU - Esnault, S
AU  - Esnault S
FAU - Shin, H C
AU  - Shin HC
FAU - Fekkar, H
AU  - Fekkar H
FAU - Guenounou, M
AU  - Guenounou M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (RNA, Messenger)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9012-63-9 (Cholera Toxin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Cholera Toxin/immunology
MH  - Cyclic AMP/*immunology/metabolism
MH  - Down-Regulation/immunology
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Interferon-gamma/*biosynthesis/genetics
MH  - Interleukin-10/*biosynthesis/genetics
MH  - Nitric Oxide Synthase/*biosynthesis/genetics
MH  - Pentoxifylline/immunology
MH  - RNA, Messenger/genetics
MH  - Signal Transduction/immunology
MH  - T-Lymphocytes/*immunology
MH  - Tumor Cells, Cultured
PMC - PMC1364004
EDAT- 1997/07/01 00:00
MHDA- 1997/09/25 00:01
PMCR- 1998/07/01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/09/25 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
PHST- 1998/07/01 00:00 [pmc-release]
AID - 10.1046/j.1365-2567.1997.00260.x [doi]
PST - ppublish
SO  - Immunology. 1997 Jul;91(3):361-8. doi: 10.1046/j.1365-2567.1997.00260.x.