Involvement of protein kinase A in histamine-mediated inhibition of IL-2 mRNA expression in mouse splenocytes

Larisa Y Poluektova, Gregory K. Huggler, Eric B. Patterson, Manzoor M. Khan

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 μM), an inhibitor of PKA regulatory subunit. The cells were then washed thoroughly and activated with plate-bound anti-CD3 (5 μg/ml), or PHA (1:100) or PMA+ionomycin (10 ng/ml, 1 μg/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. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)77-87
Number of pages11
JournalImmunopharmacology
Volume41
Issue number2
DOIs
StatePublished - Feb 1 1999

Fingerprint

Cyclic AMP-Dependent Protein Kinases
Histamine
Interleukin-2
Messenger RNA
Ionomycin
Protein Kinases
Histamine Agents
CD3 Antigens
T-Lymphocytes
Histamine H2 Receptors
Basophils
Histamine Release
Protein Kinase Inhibitors
T-Cell Antigen Receptor
Adenylyl Cyclases
Mast Cells
Protein Kinase C
Signal Transduction
Hypersensitivity
Antigens

Keywords

  • Histamine
  • Interleukin-2
  • Protein kinase A
  • Rp-cAMPS

ASJC Scopus subject areas

  • Pharmacology

Cite this

Involvement of protein kinase A in histamine-mediated inhibition of IL-2 mRNA expression in mouse splenocytes. / Poluektova, Larisa Y; Huggler, Gregory K.; Patterson, Eric B.; Khan, Manzoor M.

In: Immunopharmacology, Vol. 41, No. 2, 01.02.1999, p. 77-87.

Research output: Contribution to journalArticle

Poluektova, Larisa Y ; Huggler, Gregory K. ; Patterson, Eric B. ; Khan, Manzoor M. / Involvement of protein kinase A in histamine-mediated inhibition of IL-2 mRNA expression in mouse splenocytes. In: Immunopharmacology. 1999 ; Vol. 41, No. 2. pp. 77-87.
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