Histamine enhances interleukin (IL)-1-induced IL-1 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells. Comparison with IL-1 receptor antagonist. 1993

E Vannier, and C A Dinarello
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111.

Histamine and IL-1 have been implicated in the pathogenesis of chronic inflammatory diseases, such as pulmonary allergic reactions and rheumatoid arthritis. We therefore investigated whether histamine modulated the synthesis of IL-1 beta. Human PBMC were stimulated with IL-1 alpha (10 ng/ml) in the absence or presence of histamine (10(-9)-10(-4) M). Histamine alone did not induce protein synthesis or mRNA accumulation for IL-1 beta. IL-1 alpha-induced IL-1 beta synthesis was enhanced two to threefold by histamine concentrations from 10(-6)-10(-4) M. Cimetidine, an H2 receptor antagonist, reversed the histamine (10(-5) M)-mediated increase in IL-1 alpha-induced IL-1 beta synthesis. Diphenhydramine, an H1 receptor antagonist, had no effect. Indomethacin, a cyclooxygenase inhibitor, significantly reduced IL-1 alpha-induced IL-1 beta synthesis, but had no effect on the histamine-mediated increase in IL-1 alpha-induced IL-1 beta synthesis. Histamine (10(-5) M) enhanced and sustained IL-1 beta mRNA levels in IL-1 alpha-stimulated PBMC. However, histamine reduced IL-1 beta mRNA half-life (2.4 vs 1.2 h), suggesting that histamine enhances IL-1 alpha-induced IL-1 beta synthesis at the level of transcriptional activation. On the other hand, histamine (10(-5) M) did not affect IL-1 alpha-induced synthesis of IL-1 receptor antagonist. These results suggest that mast cells may sustain chronic inflammatory processes by upregulating self-induction of IL-1 through histamine release.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D011970 Receptors, Histamine H2 A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5) Histamine H2 Receptors,H2 Receptors,Receptors, H2,H2 Receptors, Histamine
D006632 Histamine An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012795 Sialoglycoproteins Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities. Polysialoglycoprotein,Sialoglycopeptide,Sialoglycopeptides,Sialoglycoprotein,Sialoprotein,Sialoproteins,Polysialoglycoproteins
D015232 Dinoprostone The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. PGE2,PGE2alpha,Prostaglandin E2,Prostaglandin E2alpha,PGE2 alpha,Prepidil Gel,Prostaglandin E2 alpha,Prostenon,E2 alpha, Prostaglandin,E2, Prostaglandin,E2alpha, Prostaglandin,Gel, Prepidil,alpha, PGE2,alpha, Prostaglandin E2
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal

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