Recombinant adenovirus encoding gp100 modulates experimental melanin-protein induced uveitis (EMIU).
Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated autoimmune uveitis induced by immunization with bovine uveal melanin protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy. This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed for histology and the left eye was analysed for cytokines by quantitative reverse transcriptase-polymerase chain reaction. Western blot analysis showed that uveal melanin-protein contains gp100. In three independent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which received Ad2CMV-gp100 before immunization than in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injection prevents the development of EMIU, at least in part, through cytokine regulation.
Chan
C C
CC
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA. ccc@helix.nih.gov
Li
Y
Y
Sun
B
B
Li
Q
Q
Matteson
D M
DM
Shen
D F
DF
Nussenblatt
R B
RB
Zhai
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D002417:Cattle; D002829:Choroid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D003673:Defective Viruses / Q000235:genetics*; D003888:Desensitization, Immunologic; D005136:Eye Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D007115:Immunization Schedule; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology / Q000633:toxicity; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014605:Uveitis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D058951:gp100 Melanoma Antigen
D016207:Cytokines; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D058951:gp100 Melanoma Antigen; D018664:Interleukin-12