Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon gamma in peripheral human blood mononuclear cells and in CD19-depleted cell subsets
Bv. Horvath et al., Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon gamma in peripheral human blood mononuclear cells and in CD19-depleted cell subsets, IMMUNOL LET, 70(2), 1999, pp. 95-99
The effect of histamine and histamine antagonists was examined on gene expr
ession and biosynthesis of bacterial endotoxin (LPS) induced interferon gam
ma (IFN gamma) both in human peripheral mononuclear cells (PMBC) and in T-c
ell enriched fractions, We found, that histamine inhibited the LPS induced
transcription of IFN I gene and biosynthesis of IFN gamma protein in PMBC a
nd also in CD19-depleted cell populations. The inhibitory effect of histami
ne could be reversed by the H2 histamine receptor (HR2) antagonists cimetid
ine and ranitidine both in PMBC and in CD19-depleted cells, but not with tr
iprolidine, an H1 receptor antagonist, suggesting that the inhibition of IF
N gamma production is mediated through H2 receptors in these cell populatio
ns. In contrast to the inhibitory effect of histamine, cimetidine alone (in
the absence of exogenous histamine) strongly stimulated both the IFN gamma
mRNA and protein production, whereas this effect was hardly seen by and ot
her H2 receptor blocker, ranitidine. This superinduction of IFN gamma gene
by cimetidine disappeared if the CD19 + cells are removed from PMBC. These
results suggest, that inhibition of IFN I gene expression by histamine is a
direct effect of histamine on H2 receptor of T lymphocytes; however, the s
uperinduction of IFN gamma by cimetidine requires the presence of other (pr
obably primarily B) cell subsets. (C) 1999 Elsevier Science B.V. All rights
reserved.