Involvement of protein kinase A in histamine-mediated inhibition of IL-2 mRNA expression in mouse splenocytes.
The release of histamine from mast cells and basophils during allergic reactions can regulate functions of T cells and may influence the nature of the immune response to a given antigen. The effects of histamine on T lymphocytes are associated with its binding to H2-receptors linked with adenylate cyclase, elevation of cAMP levels and activation of cAMP-dependent protein kinase (PKA). In this report we explore the role of PKA in histamine-mediated effects on IL-2 mRNA expression and IL-2 protein secretion. Fresh isolated mouse splenocytes (C57Bl/6) were pretreated with histamine (10(-4) M) for 1 h in the presence or absence of Rp-cAMPS (50 microM), an inhibitor of PKA regulatory subunit. The cells were then washed thoroughly and activated with plate-bound anti-CD3 (5 microg/ml), or PHA (1:100) or PMA + ionomycin (10 ng/ml, 1 microg/ml) for 6 h. Pretreatment with histamine inhibited IL-2 mRNA expression and secretion in cells activated with anti-CD3 or PMA, but not in cells activated with PMA + ionomycin. Rp-cAMPS prevented histamine-mediated suppression and did not itself affect IL-2 production. These results provide evidence that histamine affected IL-2 production when the cells were activated via the T cell receptor (TCR)/CD3 complex, but did not interfere with signal transduction pathways downstream of PKC leading to production of IL-2. These effects of histamine on IL-2 secretion and mRNA expression were mediated via PKA.
Poluektova
L Y
LY
Dept. of Pharmaceutical and Administrative Sciences, Creighton University, Omaha, NE 68178, USA.
Huggler
G K
GK
Patterson
E B
EB
Khan
M M
MM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D000906:Antibodies; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D012333:RNA, Messenger; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D015759:Ionomycin; D006632:Histamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate