Cytokine production by keratinocytes and mononuclear infiltrates in oral lichen planus

Abstract

Cytokine generation by tissue-infiltrating mononuclear cells (TIMC) and by keratinocytes (KC) was investigated in material obtained from the oral mucosal tissues of patients with oral lichen planus (OLP). Peripheral blood mononuclear cells (PBMC) and chronically inflamed and noninflamed gingival KC (CIG-KC, NOR-KC, respectively) were used as the controls. Compared to NOR-KC and CIG-KC, KC from OLP patients (OLP-KC) produced much more interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The OLP-KC superiority in the production of these cytokines was more prominent when the KC were cultured in the presence of interleukin-1 beta (IL-1 beta), lipopolysaccharide and phorbol myristate acetate. OLP-KC also produced more monocyte-chemotactic factor(s) which were not inactivated by the antibodies against GM-CSF, macrophage colony-stimulating factor and monocyte chemoattractant protein-1. TIMC in OLP tissues (OLP-TIMC) were superior to PBMC in the generation of IL-6 and GM-CSF. OLP-TIMC were stimulated to produce more TNF-alpha by IL-1 beta, IL-6 and GM-CSF, more IL-6 by IL-1 beta and GM-CSF, and more GM-CSF by IL-1 beta and IL-6 than PBMC. When compared to cytokine generation in TIMC from the chronically inflamed gingivae, more interferon-gamma, IL-6 and TNF-alpha were generated by OLP-TIMC. These results indicate that KC play a critical role in OLP, producing cytokines including monocyte-chemotactic factor(s), and that the cytokines produced by TIMC and OLP-KC through autocrine and paracrine processes enhance the local inflammatory response.