Intracellular Signal Transduction in Oral Keratinocytes and Infiltrated Lymphocytes Obtained from Patients with Oral Lichen Planus-Biochemical Analysis of the Mechanism of Enhanced Cytokine Generation from Keratinocytes and Infiltration of Lymphocytes

通过对口腔扁平苔藓（OLP）的免疫生物学检测，我们发现：1）OLP患者的角质形成细胞（OLP-KC）较正常口腔粘膜角质形成细胞（KC）分泌大量的GM-CSF，IL-6，TNF-alpha和1 L-1 β。2）OLP-KC产生的细胞因子增强外周血单核细胞（PBMC）的趋化性OLP-KC培养上清激活PBMC，使PKC活性、[Ca^2+]i、[1 P_3]i水平及蛋白酪氨酸磷酸化水平上调。粘附分子如PBMC上的CD 11 a、CD 11b和CD 18和CD 49 d及其对应物ICAM-1。OLP-KC培养上清中内皮细胞表面VCAM-1和ELAM-1的表达增加，PBMC迁移能力的增强依赖于这些粘附分子的表达。通过金属离子增强，但通过E.coli-LPS和热（42 μ C）和热休克蛋白（65 kDa）肽增强。6）KC的增强的细胞因子产生与PKC活化、蛋白酪氨酸磷酸化和NV-KB活化相关。7）CD 14不相关。这些结果表明KC产生的细胞因子通过表达粘附分子诱导PBMC迁移，外源性刺激物如热和UPS可诱导KC产生细胞因子的增加。OLP患者刺激物的具体类型以及浸润的PBMC在基底细胞损伤中的作用尚待进一步研究。在未来澄清。

By immunobiological examination in oral lichen planus (OLP), we obtained following results.1) Compared with oral keratinocytes (KC) obtained from the intact oral mucosae, KC from patients with OLP (OLP-KC) generaled larger amounts of GM-CSF, lL-6, TNF-alpha and 1L-1beta.2) Cytokines generated from OLP-KC enhanced chemotaxis of peripheral blood mononulcear cells (PBMC) and they increased migration of PBMC through monolayered blood vessel endothelial cells.3) Supernatants of OLP-KC activated PBMC, upregulating PKC activity, 1P_3 and [Ca^<2+>]i levels and protein tyrosine phosphorylation.4) Correspondingly. adhesion molecules such as CD11a, CD11b, and CD18 and CD49d on PBMC and their counterparts ICAM-1. VCAM-l and ELAM-I on endothelial cells were more expressed by supernatants of OLP-KC and the enhanced migration of PBMC depended on the expression of these adhesion molecules.5) Cytokine generation by I{C was not. enhanced by metal ions but enhanced by E.coli-LPS and heat (42ﾟC) and heat shock protein (65 kDa) peptide.6) The enhanced cytokine generation from KC was associated with PKC activation, protein tyrosine phosphorylation and NV-KB activation.7) CD14 was not. expressed on KC and activation of KC by LPS was mediated by CD59.These results indicate that cytokines generated from KC induce migration of PBMC through expression of adhesion molecules and that exaggeration of cytokine generation from KC may be induced by extrinsic stimulant such as heat and UPS.Specification of the stimulant in each patient with OLP and the role of infiltrated PBMC in the impairment of the basal cells remain to be clarified in the future.