Regulation of LFA-3 (CD58) by dexamethasone and retinoic acids in vitro

Introduction: The oral form of lichen planus (OLP) is a chronic inflammator y disease characterized by the accumulation of T cells below the basal laye r of the buccal mucosa. We have previously shown that the adhesion molecule lymphocyte function-associated antigen-3 (LFA-3; CD58) is up-regulated in lesional tissue and may play an important part in the molecular pathology o f this disease. OLP is often heated with glucocorticoids, and glucocorticol d-resistant cases with retinoid drugs. However, it is not yet known whether the pharmacological action of these drugs is mediated directly or indirect ly via LFA-3. Methods: In the present experiments we have used the technique of flow cyto metry (FCM) to accurately measure the effects of the glucocorticoid dexamet hasone (DEX), all-trans retinoic acid (ATRA) and 13-cis retinoic acid (13RA ) on LFA-3 expression by three main cell types found in OLP lesions - an or al epithelial cell line (KB cells), a T lymphocyte cell line (Jurkat cells) and an antigen presenting myelomonocytic cell line (U937 cells). The relat ive levels of the specific receptors for the drugs were also determined in these cell lines using FCM. Results: ATRA and 13RA were found to have a more pronounced inhibitory effe ct on LFA-3 expression than did DEX, the U937 cells being the most sensitiv e and the KB cells the least affected. The KB cells also expressed the lowe st relative levels of drug receptors. Discussion: The results showed that the three drugs differentially down-reg ulated LFA-3 expression by each of the cell lines. Moreover, the relative i nhibitory effects of the drugs appeared to be related to the relative expre ssion of the specific drug receptors by each of the cells. Our findings sug gest that the down-regulation of LFA-3 in vitro might explain at least part ly the efficacy of glucocorticoids and retinoids in the treatment of inflam matory diseases in vivo.