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

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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.