Regulation of human leukocyte antigen expression in human conjunctival epithelium.
OBJECTIVE
To demonstrate that interferon-gamma (IFN-gamma) is the key cytokine responsible for the upregulation of HLA-DR antigen in conjunctival epithelial 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 expression. With a conjunctival epithelial cell line (ChWK), HLA-DR regulation by various cytokines was evaluated, and confocal immunocytochemical and western blot analyses were performed to evaluate the activation of nuclear factorkappa B (NF-kappaB) and signal transducers and activators of transcription 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 subject. IFN-gamma was the only cytokine that effectively upregulated HLA-DR expression in ChWK, which was synergistically enhanced by tumor necrosis factor-alpha (TNF-alpha). IFN-gamma induced the nuclear translocation of NF-kappaB, 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-kappaB.
Tsubota
K
K
Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.
Fukagawa
K
K
Fujihara
T
T
Shimmura
S
S
Saito
I
I
Saito
K
K
Takeuchi
T
T
D000328:Adult; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D016328:NF-kappa B; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma