Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using intravital microscopy, we examined the role played by B(1) receptors in leukocyte trafficking across mouse mesenteric postcapillary venules in vivo. B(1) receptor blockade attenuated interleukin (IL)-1beta-induced (5 ng intraperitoneally, 2 h) leukocyte-endothelial cell interactions and leukocyte emigration ( approximately 50% reduction). The B(1) receptor agonist des-Arg(9)bradykinin (DABK), although inactive in saline- or IL-8-treated mice, caused marked neutrophil rolling, adhesion, and emigration 24 h after challenge with IL-1beta (when the cellular response to IL-1beta had subsided). Reverse transcriptase polymerase chain reaction and Western blot revealed a temporal association between the DABK-induced response and upregulation of mesenteric B(1) receptor mRNA and de novo protein expression after IL-1beta treatment. DABK-induced leukocyte trafficking was antagonized by the B(1) receptor antagonist des-arg(10)HOE 140 but not by the B(2) receptor antagonist HOE 140. Similarly, DABK effects were maintained in B(2) receptor knockout mice. The DABK-induced responses involved the release of neuropeptides from C fibers, as capsaicin treatment inhibited the responses. Treatment with the neurokinin (NK)(1) and NK(3) receptor antagonists attenuated the responses, whereas NK(2), calcitonin gene-related peptide, or platelet-activating factor receptor antagonists had no effect. Substance P caused leukocyte recruitment that, similar to DABK, was inhibited by NK(1) and NK(3) receptor blockade. Mast cell depletion using compound 48/80 reduced DABK-induced leukocyte trafficking, and DABK treatment was shown histologically to induce mast cell degranulation. DABK-induced trafficking was inhibited by histamine H(1) receptor blockade. Our findings provide clear evidence that B(1) receptors play an important role in the mediation of leukocyte-endothelial cell interactions in postcapillary venules, leading to leukocyte recruitment during an inflammatory response. This involves activation of C fibers and mast cells, release of substance P and histamine, and stimulation of NK(1), NK(3), and H(1) receptors.
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PMID:Association between kinin B(1) receptor expression and leukocyte trafficking across mouse mesenteric postcapillary venules. 1093 25

Histamine modulates an immunological response through stimulation of appropriate receptor--H1R proinflammatory or H2R suppressive. The participation of histamine in regulation of an immunological response in the course of neoplastic disease is determined by the expression of particular receptor. The aim of our work was the investigation of the expression of mRNA of two types of histamine receptors in peripheral blood lymphocytes and the evaluation of skin-prick test with histamine in lung cancer patients before and after surgery. The investigation was performed on 15 patients qualified to surgery before and 7-10 days after treatment and on 12 healthy subjects. Reverse transcriptase polymerase chain reaction (RT-PCR) with primers labeled with fluorescent dyes was performed. Intensity of fluorescence was expressed as relative fluorescence units (RFU). The data were analysed using ABI Prism 310 GeneScan collection software Version 3.1. Skin-prick test with histamine was evaluated after 10 min by measuring the diameter of the weal. The expression of H1R and H2R mRNA in healthy subjects was not significantly different in contrast to the lung cancer patients in which a significant prevalence of H2R mRNA expression was observed before surgery and only slightly decreased after (P < 0.001). Skin-prick test--negative in one patient before surgery, after treatment was positive in all patients and the diameter of histamine weal was significantly increased (P < 0.001). One may assume that the prevalence of the expression of H2R mRNA in patients reflects the status of immunosuppression caused by cancer. Since histamine exerts its suppressive activity trough H2R it seems reasonably to include the antagonists of this receptor to the cancer therapy which may restore a relative balance between accessibility of both types of histamine receptors.
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PMID:Skin reactivity to histamine and expression of histamine receptors mRNA in lymphocytes of healthy subjects and non-small-cell lung cancer patients before and after surgery. 1519 32

Histamine is an important mediator in immune responses, but it is unclear whether periodontal tissues express histamine receptors and are able to respond to histamine. We hypothesized that histamine, inflammatory cytokines, and bacterial components released in inflamed periodontal tissues may be synergistically involved in periodontitis. The present study showed that human gingival fibroblasts mainly express histamine receptor H1R, and responded to histamine to produce interleukin (IL)-8. Stimulation of gingival fibroblasts with tumor necrosis factor-alpha, IL-1alpha, and lipopolysaccharide markedly induced IL-8 production, and the IL-8 production was synergistically augmented in the presence of or pre-treatment with histamine. Selective inhibitors of mitogen-activated protein kinases (MAPKs), nuclear factor (NF)-kappaB, and phospholipase C (PLC) significantly inhibited the synergistic effect. These results indicate that histamine induces IL-8 production from gingival fibroblasts through H1R, and synergistically augments the inflammatory stimuli by amplification of the MAPK and NF-kappaB through H1R-linked PLC. Abbreviations used: HDC, histidine decarboxylase; LPS, lipopolysaccharide; IL, interleukin; TNF, tumor necrosis factor; HR, histamine receptor; PLC, phospholipase C; MAPK, mitogen-activated protein kinase; NF, nuclear factor; ERK, extracellular signal-related kinase; JNK, c-Jun N-terminal kinase; R, receptor; TLR, Toll-like receptor; alpha-MEM, alpha-minimum essential medium; FCS, fetal calf serum; RT-PCR, reverse-transcriptase polymerase chain-reaction; ELISA, enzyme-linked immunosorbent assay; SD, standard deviation; LDH, lactate dehydrogenase.
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PMID:Histamine amplifies immune response of gingival fibroblasts. 1795 1