Regulation of human leukocyte antigen expression in human conjunctival epithelium

PURPOSE. To demonstrate that interferon-gamma (IFN-gamma) is the key cytoki ne responsible for the upregulation of HLA-DR antigen in conjunctival epith elial cells of Sjogren syndrome (SS) patients. METHODS. Flow cytometry of conjunctival epithelial cells from SS and non-SS dry eye patients was performed for the quantification of HLA-DR surface ex pression. With a conjunctival epithelial cell line (ChWK), HLA-DR regulatio n by various cytokines was evaluated, and confocal immunocytochemical and w estern blot analyses were performed to evaluate the activation of nuclear f actor-kappa B (NF-kappa B) and signal transducers and activators of transcr iption 1 and 3 (STAT1 and STAT3, respectively). RESULTS. HLA-DR expression was upregulated in conjunctival epithelial cells of SS patients but not in non-SS dry eye patient or healthy control subjec t. IFN-gamma was the only cytokine that effectively upregulated HLA-DR expr ession in ChWK, which was synergistically enhanced by tumor necrosis factor -alpha (TNF-alpha). IFN-gamma induced the nuclear translocation of NF-kappa B, but did not activate STAT1 or STAT3 in ChWK. CONCLUSIONS. Upregulation of HLA-DR antigen in the conjunctival epithelium of SS patients may be regulated by IFN-gamma through the activation of NF-k appa B.