Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen-induced uveitis

Charlotte, Frédéric; Ito, Shinji; Wu, Guey-Shuang; Kimoto, Takashi; Rao, Narsing A.

doi:10.1076/ceyr.26.1.1.14250

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…However, the RNS producer iNOS is reported to be dispensable for EAU pathogenesis, as iNOS knockout mice develop EAU with scores and cellular responses similar to wild-type mice after IRBP immunization [42]. Nevertheless, a highly selective inhibitor of iNOS enhances the EAU induced by S-antigen [43]. We also found that unlike other cytokines, IFN-γ was not induced in the EAU group.…”

Section: Discussionmentioning

confidence: 62%

Suppression of the Reactive Oxygen Response Alleviates Experimental Autoimmune Uveitis in Mice

Hsu

Yang

Teng

et al. 2020

IJMS

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Reactive oxygen species (ROS) are produced by host phagocytes and play an important role in antimicrobial actions against various pathogens. Autoimmune uveitis causes blindness and severe visual impairment in humans at all ages worldwide. However, the role of ROS in autoimmune uveitis remains unclear. We used ROS-deficient (Ncf1−/−) mice to investigate the role of ROS in experimental autoimmune uveitis (EAU). Besides, we also used the antioxidant N-acetylcysteine (NAC) treatment to evaluate the effect of suppression of ROS on EAU in mice. The EAU disease scores of Ncf1−/− mice were significantly lower than those of wild-type mice. EAU induction increased the levels of cytokines (interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-12, IL-17, and tumor necrosis factor (TNF)-α) and chemokines (monocyte chemoattractant protein (MCP)-1) in the retinas of wild-type mice but not in those of Ncf1−/− mice. EAU induction enhanced the level of NF-κB activity in wild-type mice. However, the level of NF-κB activity in Ncf1−/− mice with EAU induction was low. Treatment with the antioxidant NAC also decreased the severity of EAU in mice with reduced levels of oxidative stress, inflammatory mediators, and NF-κB activation in the retina. We successfully revealed a novel role of ROS in the pathogenesis of EAU and suggest a potential antioxidant role for the treatment of autoimmune uveitis in the future.

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Section: Discussionmentioning

confidence: 62%

Suppression of the Reactive Oxygen Response Alleviates Experimental Autoimmune Uveitis in Mice

Hsu

Yang

Teng

et al. 2020

IJMS

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“…Dal Secco et al 22 reporterd that selective inhibitors of iNOS and endothelial NOS increase leukocyte rolling and adhesion to endothelial cells and increase neutrophil transmigration to sites of inflammation. In addition, Charlotte et al 23 demonstrated that iNOS expressed in the outer retina might play a protective role in experimental autoimmune uveitis. In the current study, leukocyte rolling and migration in the immunosuppressed iNOS −/− mouse retina were dramatically suppressed compared with the normal mouse retina after lipopolysaccharide injection.…”

Section: Discussionmentioning

confidence: 99%

Lack of inducible nitric oxide synthases attenuates leukocyte-endothelial cell interactions in retinal microcirculation

Iwama

Miyahara

Tamura

et al. 2008

British Journal of Ophthalmology

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Aim:To investigate the effect of inducible nitric oxide synthases (iNOS) on inflammatory reactions during endotoxin-induced uveitis (EIU) in mice by studying leukocyte–endothelial cell interactions.Methods:EIU was produced in immunosuppressed iNOS−/− mice and C57BL/6 (normal) mice by footpad injection of lipopolysaccharide. Leukocytes were labelled with acridine orange. Leukocyte rolling in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. The number of migrated leukocytes was counted in flat-mounted retina.Results:Both leukocyte rolling and migration peaked at 48 h after lipopolysaccharide injection. The maximal numbers of rolling leukocytes in the immunosuppressed iNOS−/− mouse retina decreased by 98.2% (p<0.001) compared with that in the normal mouse retina at 48 h after lipopolysaccharide injection. In addition, the maximal numbers of migrated leukocytes in the immunosuppressed iNOS−/− mouse retina decreased by 74.0% (p<0.001) compared with that in the normal mouse retina at 24 h after lipopolysaccharide injection. Furthermore, the diameters of major retinal veins of the immunosuppressed iNOS−/− group were smaller at both 24 and 48 h after lipopolysaccharide injection than were those of the normal group (p<0.001, respectively).Conclusions:A lack of iNOS suppresses leukocyte–endothelial cell interactions in the retinas of mice with EIU. This suggests that iNOS may play a role in the management of patients with uveitis and other inflammatory conditions.

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Constitutive and Cytokine-Induced GITR Ligand Expression on Human Retinal Pigment Epithelium and Photoreceptors

Kim

Fariss

et al. 2004

Invest. Ophthalmol. Vis. Sci.

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Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen-induced uveitis

Abstract: The data suggests that 1400 W exacerbates choroidal inflammation and photoreceptor damage at the effector phase of S-antigen-induced uveitis. This implies that iNOS expressed in the outer retina may have a protective role in EAU.

Cited by 5 publications

References 11 publications

Suppression of the Reactive Oxygen Response Alleviates Experimental Autoimmune Uveitis in Mice

Suppression of the Reactive Oxygen Response Alleviates Experimental Autoimmune Uveitis in Mice

Lack of inducible nitric oxide synthases attenuates leukocyte-endothelial cell interactions in retinal microcirculation

Constitutive and Cytokine-Induced GITR Ligand Expression on Human Retinal Pigment Epithelium and Photoreceptors

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