Okabe T, Hide M, Koro O, Yamamoto S
Department of Dermatology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minamiku, 734-8551, Hiroshima, Japan.
Eur J Pharmacol. 2000 Jun 16;398(2):309-15. doi: 10.1016/s0014-2999(00)00304-6.
Substance P plays an important role in neurogenic inflammation with granulocyte infiltration. To investigate cytokines involved in the substance P-induced inflammation and the mechanism of cell activation, we studied the release of TNF (tumor necrosis factor)-alpha and histamine from human skin slices in response to substance P and antigen. Substance P induced the release of histamine and TNF-alpha in a dose-dependent manner at concentrations from 0.8 to 100 microM. PD 098059 (2'-amino-3'-methoxyflavone) selectively inhibited the release of TNF-alpha, but not the release of histamine induced by either substance P or antigen. SB 203580 ([4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-++ +imida zole]) slightly inhibited TNF-alpha release induced by antigen, but not that induced by substance P, and slightly enhanced histamine release induced by either stimulation. The release of TNF-alpha in response to either stimulation was inhibited by 1 nM-1 microM dexamethasone, but histamine release was not affected. These results suggest that substance P, in addition to antigen, induced TNF-alpha release from human skin by a mitogen-activated protein (MAP) kinase, predominantly extracellular signaling-regulated protein kinase (ERK)-dependent, and dexamethasone-sensitive pathway, which is separate from that for histamine release from mast cells.
P物质在伴有粒细胞浸润的神经源性炎症中起重要作用。为了研究参与P物质诱导炎症的细胞因子以及细胞活化机制，我们研究了人皮肤切片对P物质和抗原反应时肿瘤坏死因子（TNF）-α和组胺的释放情况。P物质在0.8至100微摩尔浓度范围内以剂量依赖方式诱导组胺和TNF-α的释放。PD 098059（2'-氨基-3'-甲氧基黄酮）选择性抑制TNF-α的释放，但不抑制P物质或抗原诱导的组胺释放。SB 203580（[4-（4-氟苯基）-2-（4-甲基亚磺酰基苯基）-5-（4-吡啶基）1H-咪唑]）轻微抑制抗原诱导的TNF-α释放，但不抑制P物质诱导的释放，且轻微增强两种刺激诱导的组胺释放。1纳摩尔至1微摩尔的地塞米松抑制两种刺激引起的TNF-α释放，但不影响组胺释放。这些结果表明，P物质除了抗原外，还通过丝裂原活化蛋白（MAP）激酶，主要是细胞外信号调节蛋白激酶（ERK）依赖性和地塞米松敏感途径，诱导人皮肤释放TNF-α，这与肥大细胞释放组胺的途径不同。
