Histamine Amplifies Immune Response of Gingival Fibroblasts
Histamine Amplifies Immune Response of Gingival Fibroblasts
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DOI：
10.1177/154405910708601112
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发表时间：
2007-11
影响因子：
7.6
通讯作者：
T. Minami;T. Kuroishi;Akiko Ozawa;H. Shimauchi;Yasuo Endo;Shunji Sugawara
中科院分区：
文献类型：
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作者：
T. Minami;T. Kuroishi;Akiko Ozawa;H. Shimauchi;Yasuo Endo;Shunji Sugawara
组胺是免疫反应中的重要介质，但牙周组织是否表达组胺受体并能够对组胺作出反应尚不清楚。我们推测，组织胺，炎症细胞因子和细菌成分释放在发炎的牙周组织可能协同参与牙周炎。本研究表明，人牙龈成纤维细胞主要表达组胺受体H1 R，并对组胺产生应答，产生白细胞介素（IL）-8。用肿瘤坏死因子-α、IL-1α和脂多糖刺激牙龈成纤维细胞显着诱导IL-8的产生，并且在组胺存在或预处理的情况下，IL-8的产生协同增加。丝裂原活化蛋白激酶（MAPK）、核因子（NF）-κB和磷脂酶C（PLC）的选择性抑制剂可显著抑制协同效应。这些结果表明，组胺通过H1 R诱导牙龈成纤维细胞产生IL-8，并通过H1 R连接的PLC通过MAPK和NF-κB的扩增协同增强炎症刺激。NF，核因子; ERK，细胞外信号相关激酶; JNK，c-Jun N-末端激酶; R，受体; TLR，Toll样受体; α-MEM，α-最低必需培养基; FCS，胎牛血清; RT-PCR，逆转录酶聚合酶链反应; ELISA，酶联免疫吸附试验; SD，标准差; LDH，乳酸脱氢酶。
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-α, IL-1α, 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)-κB, 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-κB 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; α-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.