Background Nucleotide-binding oligomerization domain (NOD) - containing 2 (NOD2) is a NOD - like receptors (NLRs) which plays important role in immune regulation and inflammatory response. There are increasing evidences to show that NOD2 may contribute to the development of numerous auto inflammatory and autoimmune disorders. However, their role in lupus nephritis (LN) is not known. Here, we explored the role of NOD2 in LN.
Objectives However, their role in lupus nephritis (LN) is not known. Here, we explored the role of NOD2 in LN.
Methods Immunohistochemistry was applied to observe the expression of NOD2 in renal biopsies. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of NOD2 mRNA in the biopsies. In vitro studies, HK-2 cells (renal tubular epithelial cell-line) were cultured with different inflammatory stimulation, western blot was used to investigate their expression of NOD2 and the following activation of MAPK pathway signals (ERK1/2, p38 and JNK), real-time qPCR was applied to observe the mRNA levels of downstream pro-inflammatory mediators (IL-1b, IL-8, MCP-1, TGF-b1, IL-6).
Results (1) Immunohistochemistry staining demonstrated that the expression of NOD2 in LN is higher than that of normal control (P=0.002), and the mRNA level of NOD2 in renal tissue of LN patients was higher than that of normal control (P=0.001). (2) In vitro studies, the urine and serum from onset LN patients can significantly promote higher NOD2 expression in HK2 cells than that from healthy control (P<0.001). In addition, TGF-b1, LPS and muramyl dipeptide (MDP) can also induce higher NOD2 expression in HK2 cells (P<0.001, respectively). (3) The activation of NOD2 increased phosphorylation of ERK1/2, p38 and JNK. Moreover, the activation of NOD2 induced the release of pro-inflammatory mediators including IL-1b, IL-8, MCP-1, TGF-b1, IL-6.
Conclusions Our study showed NOD2 expression was increased in LN patients. The activation of NOD2 can promote the activation of MAPK signaling pathway and release of downstream pro-inflammatory mediators. NOD2 may participate in the pathogenesis of LN.
Disclosure of Interest None declared