The effects of histamine on interferon gamma production are dependent on the stimulatory signals

Natalia Osna, Kathleen Elliott, Manzoor M. Khan

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Histamine regulates the immune response by enhancing TH2 cytokine production and by inhibiting TH1 cytokine production. We assessed the mechanisms of histamine's action on helper T cell subsets by evaluating the role of protein kinase A (PKA) in the histamine-mediated effects on IFNγ production. The splenocytes and TH1 murine cloned cells (pGL10) were pretreated with histamine at a concentration range of 10-8-10-5 M for 1 h and then were activated with anti-CD3, PHA, PMA + ionomycin, or ionomycin for 24 h. The levels of IFNγ were measured in the supernatants by ELISA. The inhibitory effects of histamine were the most prominent in anti-CD3-stimulated splenocytes (61%). The effects of histamine on IFNγ production from TH1 cells depended on the mode of cell activation. The activation of cells with anti-CD3 resulted in 27% inhibition of IFNγ production whereas the activation with ionomycin produced 70% suppression. The inhibitory effects of histamine were completely reversed by cimetidine in a dose-dependent manner in both TH1 cells and in splenocytes. PKA played a role in the inhibition of IFNγ by histamine when the cells were activated via TCR, and the PKA inhibitors Rp-cAMPS (10-5 M) and H8 (10-5 M) reversed the inhibitory effects of histamine on IFNγ production. However, when the cells were stimulated with ionomycin, the PKA inhibitors did not affect histamine-mediated suppression of IFNγ production.

Original languageEnglish (US)
Pages (from-to)135-145
Number of pages11
JournalInternational Immunopharmacology
Volume1
Issue number1
DOIs
StatePublished - Mar 15 2001

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Histamine
Interferon-gamma
Ionomycin
Cyclic AMP-Dependent Protein Kinases
Protein Kinase Inhibitors
Histamine Agents
Cytokines
Cimetidine
T-Lymphocyte Subsets
Helper-Inducer T-Lymphocytes
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

The effects of histamine on interferon gamma production are dependent on the stimulatory signals. / Osna, Natalia; Elliott, Kathleen; Khan, Manzoor M.

In: International Immunopharmacology, Vol. 1, No. 1, 15.03.2001, p. 135-145.

Research output: Contribution to journalArticle

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