NLRC3 promotes host resistance against Pseudomonas aeruginosa-induced keratitis by promoting the degradation of IRAK1

Guo,Litao; Kong,Qingzhu; Dong,Zhijun; Dong,Weili; Fu,Xiaoxiao; Su,Leqi; Tan,Xiaobo

doi:10.3892/ijmm.2017.3077

NLRC3 promotes host resistance against Pseudomonas aeruginosa-induced keratitis by promoting the degradation of IRAK1

Authors:
- Litao Guo
- Qingzhu Kong
- Zhijun Dong
- Weili Dong
- Xiaoxiao Fu
- Leqi Su
- Xiaobo Tan
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Affiliations: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, P.R. China, Department of Orthopedic Trauma, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, P.R. China, Graduate School of Chengde Medical University, Chengde, Hebei 067000, P.R. China
Published online on: July 20, 2017 https://doi.org/10.3892/ijmm.2017.3077
Pages: 898-906

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Abstract

Pseudomonas aeruginosa (PA)-induced keratitis is one of the most common and destructive bacterial diseases. The pathogenesis of PA infections is closely associated with excessive inflammatory responses. Nucleotide oligomerization domain (NOD)-like receptor (NLR) family with caspase activation and recruitment domain (CARD) containing 3 (NLRC3) protein has been implicated as a negative regulator of inflammation and antiviral response, but the role of NLRC3 in PA-induced keratitis has not been described. In the present study, we investigated the effects of NLRC3 in PA-induced keratitis and explored the underlying mechanism. We found that the expression of NLRC3 was decreased in mouse corneas and macrophages after PA infection. Overexpression of NLRC3 significantly attenuated disease progression, inhibited the activation of nuclear factor-κB signaling and decreased the production of pro-inflammatory cytokines after PA infection. Furthermore, overexpression of NLRC3 promoted K48-linked polyubiquitination and degradation of interleukin-1 receptor-associated kinase 1 (IRAK1). Taken together, we demonstrated that NLRC3 has an anti-inflammatory effect on PA-induced keratitis, which may provide an improved understanding of host resistance to PA infection.

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