Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine inhibited the proliferative response of human peripheral blood mononuclear cells (PBMC) to the T cell mitogen Phytohemagglutinin-P (PHA-P) in a dose-dependent fashion. This inhibition was mediated via the H2 receptor since cimetidine, a known H2 antagonist, removed the inhibition, whereas the addition of the H1 antagonist Diphenhydramine did not. Inhibition occurred during the inductive phase of the cell cycle, since histamine added 24 hours after PHA-P stimulation had no effect on subsequent T cell proliferation, and was attributable to inhibition of interleukin-2 (IL-2) gene expression. Both secreted IL-2 and messenger RNA coding for IL-2 were inhibited by histamine. In contrast, histamine exerted no inhibitory effect on the expression of cell surface receptors for IL-2 as determined by flow cytometry. Furthermore, histamine-treated cells retained full responsiveness to exogenously administered IL-2, which completely reversed the anti-proliferative effect of histamine. In some donors, histamine enhanced the percentage of IL-2 receptor positive cells. Stimulated PBMC from AIDS KS patients as a group, displayed a lower percentage of IL-2 receptor bearing cells, which was significantly increased by the addition of histamine even at concentrations as low as 10(-6) M and peaking at 10(-3) M. These findings indicate that histamine exerts its anti-proliferative effects on T cells by inhibiting IL-2 production, via blockade of IL-2 gene expression. In addition, histamine seems to exert immunomodulating effects on IL-2 receptor expression, particularly in those individuals with AIDS-KS.
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PMID:Histamine blocks interleukin 2 (IL-2) gene expression and regulates IL-2 receptor expression. 226 28

We have studied the effects of histamine on the proliferation and the intracellular cyclic adenosine monophosphate (cAMP) levels of T-lymphocyte clones (TLC) generated from bronchoalveolar lavage fluid (BALF) or peripheral blood (PB) from healthy and asthmatic persons. TLC from either compartment and from both groups of donors were heterogeneous in their response to histamine. In BALF-derived TLC, three types of responses were observed: histamine inhibited, stimulated, or did not modulate the anti-CD3-induced proliferation. Histamine directly and dose dependently inhibited the anti-CD3-induced proliferation of six (two asthmatic) of 12 CD4+ BALF TLC, stimulated two BALF TLC (both nonasthmatic), and did not modulate the proliferation of four BALF TLC. The maximal inhibition was 70%, the maximal stimulation 200%, both at 10(-3) M histamine. The stimulation of proliferation was associated with increased interleukin-2 (IL-2) production, whereas the inhibition of proliferation was associated with decreased IL-2 production and downregulation of IL-2 receptor expression. The inhibitory effects could be partly reversed by H2-receptor antagonists and could be mimicked by an H2-receptor agonist. In contrast, the stimulatory effect was not reversed or mimicked by H1 or H2 antagonists or agonists. The majority of CD4+ TLC responded to histamine with a rise in the intracellular cAMP levels. A rise in cAMP, however, was often but not always associated with an inhibition of proliferation. In addition, stimulation of proliferation occurred in the absence of a rise in cAMP. We compared cAMP rises in panels of TLC obtained with high cloning efficiencies from the PB from a healthy person and from an asthmatic person.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterogeneous effects of histamine on proliferation of lung- and blood-derived T-cell clones from healthy and asthmatic persons. 832 49