Regulation of LFA-3 (CD58) by dexamethasone and retinoic acids in vitro.
BACKGROUND
The oral form of lichen planus (OLP) is a chronic inflammatory disease characterized by the accumulation of T cells below the basal layer 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 of this disease. OLP is often treated with glucocorticoids, and glucocorticoid-resistant cases with retinoid drugs. However, it is not yet known whether the pharmacological action of these drugs is mediated directly or indirectly via LFA-3.


METHODS
In the present experiments we have used the technique of flow cytometry (FCM) to accurately measure the effects of the glucocorticoid dexamethasone (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 oral epithelial cell line (KB cells), a T lymphocyte cell line (Jurkat cells) and an antigen presenting myelomonocytic cell line (U937 cells). The relative 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 effect on LFA-3 expression than did DEX, the U937 cells being the most sensitive and the KB cells the least affected. The KB cells also expressed the lowest relative levels of drug receptors.


CONCLUSIONS
The results showed that the three drugs differentially down-regulated LFA-3 expression by each of the cell lines. Moreover, the relative inhibitory effects of the drugs appeared to be related to the relative expression of the specific drug receptors by each of the cells. Our findings suggest that the down-regulation of LFA-3 in vitro might explain at least partly the efficacy of glucocorticoids and retinoids in the treatment of inflammatory diseases in vivo.
Cahen
P
P
Department of Oral Medicine, Eastman Dental Institute, University College London, UK.
Kirby
A C
AC
Porter
S R
SR
Olsen
I
I
D018968:CD58 Antigens / Q000032:analysis*; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology; D019169:Jurkat Cells; D007624:KB Cells; D011965:Receptors, Glucocorticoid / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000032:analysis; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology*; D020298:U937 Cells
D018968:CD58 Antigens; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D003907:Dexamethasone; D015474:Isotretinoin