Minami T, Kuroishi T, Ozawa A, Shimauchi H, Endo Y, Sugawara S
Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
J Dent Res. 2007 Nov;86(11):1083-8. doi: 10.1177/154405910708601112.
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.
组胺是免疫反应中的一种重要介质，但尚不清楚牙周组织是否表达组胺受体以及能否对组胺作出反应。我们推测，在炎症性牙周组织中释放的组胺、炎性细胞因子和细菌成分可能协同参与牙周炎的发生。本研究表明，人牙龈成纤维细胞主要表达组胺受体H1R，并对组胺作出反应产生白细胞介素（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可显著诱导IL-8的产生，并且在存在组胺或用组胺预处理的情况下，IL-8的产生会协同增加。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这种协同效应。这些结果表明，组胺通过H1R诱导牙龈成纤维细胞产生IL-8，并通过与H1R相关的PLC放大MAPK和NF-κB来协同增强炎症刺激。使用的缩写：HDC，组氨酸脱羧酶；LPS，脂多糖；IL，白细胞介素；TNF，肿瘤坏死因子；HR，组胺受体；PLC，磷脂酶C；MAPK，丝裂原活化蛋白激酶；NF，核因子；ERK，细胞外信号相关激酶；JNK，c-Jun氨基末端激酶；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，逆转录聚合酶链反应；ELISA，酶联免疫吸附测定；SD，标准差；LDH，乳酸脱氢酶。
