The mechanism of mononuclear cell infiltration in oral lichen planus: the role of cytokines released from keratinocytes.
To clarify the pathogenesis of oral lichen planus (OLP), we investigated the roles of keratinocytes (KC) in mononuclear cell infiltration. When peripheral blood mononuclear cells (PBMC) obtained from healthy donors were cultured in the presence of culture supernatants of KC separated from the noninflamed gingivae (Nor-KC) and cheek mucosae of patients with OLP (OLP-KC), the number of migrated PBMC across monolayered human umbilical vein endothelial cells (HUVEC) were increased to about 1.3-fold and 1.5-fold of the control level, respectively, with increases of the expression of CD11a, CD11b, CD18, and CD49d on PBMC and intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 on HUVEC. The number of migrated PBMC was reduced to about 60% of the control level by pretreatment of PBMC with anti-CD11a or anti-CD18 MAb and reduced to about 70% by pretreatment of HUVEC with anti-CD54 MAb. The pretreatment of PBMC with genistein, H-7, wortmannin, or exoenzyme C3 decreased the migrated PBMC by about 70 to 90%. In agreement with these results, the culture supernatants of OLP-KC up-regulated tyrosine phosphorylation of 62-kDa, 70-kDa, and 102-kDa proteins, phosphatidylinositol-3 kinase, and protein kinase C activities and activated Rho protein level more so than did those of Nor-KC. Additionally, actin reorganization with the formation of membrane ruffles and lamellipodia was distinctly induced by the culture supernatants of OLP-KC. These results indicate that cytokines generated by KC transduce their signals in PBMC, up-regulating the expression of cell surface adhesion molecules and migration activity with reorganization of actin filaments.
Department of Oral Surgery, Kochi Medical School, Kohasu, Nankoku-city, Japan.
T
T
Yamamoto
T
T
Nakane
T
T
Osaki
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000199:Actins / Q000187:drug effects / Q000648:ultrastructure; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects; D002630:Chemotactic Factors / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000378:metabolism*; D003599:Cytoskeleton / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D015603:Keratinocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D017676:Lichen Planus, Oral / Q000276:immunology* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology; D009061:Mouth Mucosa / Q000276:immunology / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction; D014471:Umbilical Veins; D020741:rho GTP-Binding Proteins / Q000502:physiology
D000199:Actins; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016207:Cytokines; D004791:Enzyme Inhibitors; D016169:Lymphocyte Function-Associated Antigen-1; D047428:Protein Kinase Inhibitors; D018799:Intercellular Adhesion Molecule-1; D006160:Guanosine Triphosphate; D011494:Protein Kinases; D020741:rho GTP-Binding Proteins