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 language | English (US) |
|---|---|
| Pages (from-to) | 135-145 |
| Number of pages | 11 |
| Journal | International Immunopharmacology |
| Volume | 1 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 15 2001 |
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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 journal › Article
}
TY - JOUR
T1 - The effects of histamine on interferon gamma production are dependent on the stimulatory signals
AU - Osna, Natalia
AU - Elliott, Kathleen
AU - Khan, Manzoor M.
PY - 2001/3/15
Y1 - 2001/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035124477&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035124477&partnerID=8YFLogxK
U2 - 10.1016/S1567-5769(00)00005-9
DO - 10.1016/S1567-5769(00)00005-9
M3 - Article
C2 - 11367511
AN - SCOPUS:0035124477
VL - 1
SP - 135
EP - 145
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 1
ER -