AIMS: The aim of this study was to investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor (NF)-kappaB inhibitor, on cytokine expression and suppression of anterior chamber inflammation in experimental autoimmune anterior uveitis. Uveitis was induced in the Lewis rats with the injection of a melanin-associated antigen into the peritoneum and footpad. At defined time points, cytokine mRNA expressions in the iris and ciliary body were measured by using a semiquantitative polymerase chain-reaction method. RESULTS: We found that interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF)-alpha mRNA expression peaked during the active phase of uveitis, whereas interleukin (IL)-10 mRNA increased during the disease resolution. In a separate experiment, PDTC (100 and 200 mg/kg/day) was administrated intraperitoneally daily after immunization. We found that PDTC (100 and 200 mg/kg/day) effectively suppressed ocular inflammation, as indicated by reduced clinical scores and inflammatory cells infiltration in aqueous humor and the iris and ciliary body. CONCLUSIONS: The inhibitory effects of PDTC are mainly resulted from inhibiting the expression of proinflammatory cytokines, TNF-alpha and IFN-gamma but augmenting anti-inflammatory cytokines, IL-10 expression. These findings suggest that the application of NF-kappaB inhibitors may be a potential therapeutic method for the treatment of acute anterior uveitis.
AIMS: The aim of this study was to investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor (NF)-kappaB inhibitor, on cytokine expression and suppression of anterior chamber inflammation in experimental autoimmune anterior uveitis. Uveitis was induced in the Lewis rats with the injection of a melanin-associated antigen into the peritoneum and footpad. At defined time points, cytokine mRNA expressions in the iris and ciliary body were measured by using a semiquantitative polymerase chain-reaction method. RESULTS: We found that interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF)-alpha mRNA expression peaked during the active phase of uveitis, whereas interleukin (IL)-10 mRNA increased during the disease resolution. In a separate experiment, PDTC (100 and 200 mg/kg/day) was administrated intraperitoneally daily after immunization. We found that PDTC (100 and 200 mg/kg/day) effectively suppressed ocular inflammation, as indicated by reduced clinical scores and inflammatory cells infiltration in aqueous humor and the iris and ciliary body. CONCLUSIONS: The inhibitory effects of PDTC are mainly resulted from inhibiting the expression of proinflammatory cytokines, TNF-alpha and IFN-gamma but augmenting anti-inflammatory cytokines, IL-10 expression. These findings suggest that the application of NF-kappaB inhibitors may be a potential therapeutic method for the treatment of acute anterior uveitis.
Authors: Olga M Viquez; Holly L Valentine; Kalyani Amarnath; Dejan Milatovic; William M Valentine Journal: Toxicol Appl Pharmacol Date: 2008-01-26 Impact factor: 4.219
Authors: Holly L Valentine; Olga M Viquez; Kalyani Amarnath; Venkataraman Amarnath; Justin Zyskowski; Endalkachew N Kassa; William M Valentine Journal: Chem Res Toxicol Date: 2009-01 Impact factor: 3.739
Authors: Mohammad Shoeb; Min Zhang; Tianlin Xiao; Misha F Syed; Naseem H Ansari Journal: Invest Ophthalmol Vis Sci Date: 2018-01-01 Impact factor: 4.799