Cytokines and apoptotic molecules in experimental melanin-protein induced uveitis (EMIU) and experimental autoimmune uveoretinitis (EAU).
The cytokine profile and occurrence of apoptosis during experimental melanin-protein induced uveitis (EMIU) were investigated and compared with that of experimental autoimmune uveoretinitis (EAU). EMIU or EAU was induced in Lewis rats. Eyes were collected at different time points after immunization. Cytokine mRNA expression was identified in the inflammatory cells in the uvea of EMIU rats; IL-2, IFN-gamma and IL-12 increased at the peak of the inflammation, and then tapered off as inflammation subsided. IL-4 and IL-10 increased at the peak of ocular inflammation, and persisted with inflammation resolved. Fas and FasL were expressed consistently in ocular resident cells of EMIU, but were elevated in EAU. In EAU, Bcl-2 expression showed a sharp peak in inflammatory cells but not in the resident cells. In EMIU, high levels of Bcl-2 were present and persisted in both ocular resident and inflammatory cells. Expression of Bax was relatively stable in both EAU and EMIU. Cellular DNA fragmentation was detected in the retinal glial cells of EAU and some inflammatory cells of EMIU. In EMIU, the dynamics of Th1 cytokines were consistent with the ocular inflammation, whereas persistent expression of Th2 cytokines was consistent with their known regulatory role. The continuous high expression of Bcl-2 and the high ratio of Bcl-2 to Bax in the eyes of EMIU may possibly contribute to prevention of ocular tissue damage, and of inflammatory cells from undergoing apoptosis, thus resulting in chronic recurrent inflammation.
Li
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Q
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA.
Sun
B
B
Matteson
D M
DM
O'Brien
T P
TP
Chan
C C
CC
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008543:Melanins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000276:immunology / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014602:Uvea / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*
D016207:Cytokines; D008543:Melanins