TY - JOUR
T1 - Dual control of human interleukin-2 and interferon-γ gene expression by histamine
T2 - Activation and suppression
AU - Arad, G.
AU - Nussinovich, R.
AU - Na'Amad, M.
AU - Kaempfer, R.
PY - 1996/5/25
Y1 - 1996/5/25
N2 - Histamine is considered to be an activator of cells with suppressive capacity. In agreement with this concept, we show that histamine elicits a strong inhibition of the induced expression of interleukin-2 (IL-2) and interferon-γ (IFN-γ) genes. However, our experiments reveal a novel property of histamine: early in the induction process, it strongly stimulates expression of these two genes in cultured human peripheral blood mononuclear cells (PBMC). The histamine-mediated superinduction of IL-2 mRNA is seen also in a Th cell line, showing that such cells respond directly to histamine. In the course of mitogenic induction, a 20-fold stimulation by histamine is converted into an equally strong inhibition. The response of a PBMC population to histamine thus undergoes a remarkable change following T cell activation. The dual effect of histamine can be blocked by the H2 histamine receptor antagonist cimetidine, while the early activation by histamine is mimicked by the H2 agonist impromidine, showing that both activation and inhibition of IL-2 and IFN-γ gene expression by histamine are exerted via this receptor. These results support the concept that histamine, released during an immune response, exerts opposite regulatory effects by first activating cells able to express the IL-2 and IFN-γ genes and only then suppressive cells that become responsive to histamine more slowly, but once activated shut off the expression of these genes.
AB - Histamine is considered to be an activator of cells with suppressive capacity. In agreement with this concept, we show that histamine elicits a strong inhibition of the induced expression of interleukin-2 (IL-2) and interferon-γ (IFN-γ) genes. However, our experiments reveal a novel property of histamine: early in the induction process, it strongly stimulates expression of these two genes in cultured human peripheral blood mononuclear cells (PBMC). The histamine-mediated superinduction of IL-2 mRNA is seen also in a Th cell line, showing that such cells respond directly to histamine. In the course of mitogenic induction, a 20-fold stimulation by histamine is converted into an equally strong inhibition. The response of a PBMC population to histamine thus undergoes a remarkable change following T cell activation. The dual effect of histamine can be blocked by the H2 histamine receptor antagonist cimetidine, while the early activation by histamine is mimicked by the H2 agonist impromidine, showing that both activation and inhibition of IL-2 and IFN-γ gene expression by histamine are exerted via this receptor. These results support the concept that histamine, released during an immune response, exerts opposite regulatory effects by first activating cells able to express the IL-2 and IFN-γ genes and only then suppressive cells that become responsive to histamine more slowly, but once activated shut off the expression of these genes.
UR - http://www.scopus.com/inward/record.url?scp=0029893674&partnerID=8YFLogxK
U2 - 10.1006/cimm.1996.0145
DO - 10.1006/cimm.1996.0145
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C2 - 8660811
AN - SCOPUS:0029893674
SN - 0008-8749
VL - 170
SP - 149
EP - 155
JO - Cellular Immunology
JF - Cellular Immunology
IS - 1
ER -