Open AccessNLRC3 promotes host resistance against Pseudomonas aeruginosa-induced keratitis by promoting the degradation of IRAK1
Author(s) -
Litao Guo,
Qingzhu Kong,
Zhao Dong,
Weili Dong,
Xiaoxiao Fu,
Leqi Su,
Xiaojun Tan
Publication year - 2017
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2017.3077
Subject(s) - keratitis , pseudomonas aeruginosa , apoptosis , pathogenesis , cell cycle , biology , cancer research , microbiology and biotechnology , immunology , bacteria , genetics
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. Overexpr-ession 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.