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

Natalia Osna, Kathleen Elliott, Manzoor M. Khan

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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
Publication statusPublished - Mar 15 2001

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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