Targeting TBK1 attenuates ocular inflammation in uveitis by antagonizing NF-κB signaling
Si Chen, Jinfeng Kong, Shiying Wu, Chenqi Luo, Junhui Shen, Zhaocai Zhang, Jian Zou, Lei Feng
Journal:CLINICAL IMMUNOLOGY
IF:10.19
DOI:10.1016/j.clim.2022.109210
PMID:36528252
Published:2022-12-14
research field:免疫学炎症眼科学
Abstract
Uveitis with complex pathogenesis is a kind of eye emergency involving refractory and blinding inflammation. Dysregulation of TANK binding kinase 1 (TBK1), which plays an important role in innate immunity , often leads to inflammatory diseases in various organs. However, the role of TBK1 in uveitis remains elusive. In this study, we identified that the mRNA expression level of TBK1 and its phosphorylation level were significantly increased in peripheral blood mononuclear cells (PBMCs) of patients with uveitis. Consistent with this, the expression of Tbk1 was elevated in the ocular tissues of uveitis rats and primary peritoneal macrophages while its phosphorylation levels, which present activation forms, were upregulated as well, accompanied by an increase in the level of nuclear factor-κB (NF-κB) and proinflammatory cytokines . In addition, inhibition of TBK1 may effectively reduce the inflammatory response of uveitis rats by blocking NF-κB entry into the nucleus and impeding the initiation of NLRP3 inflammasome- and caspase-1-mediated pyroptosis pathways.
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