• Xiao-Jing Wu, Xu-Ming Yang, Xue-Min Song, Yang Xu, Jian-Guo Li, Yan-Lin Wang, Zong-Ze Zhang, Lin-Li Le, Hui Liang, and Yin Zhang.
• *Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Wuchang, Hubei Province, China †The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Wuchang, Hubei Province, China.
• Shock. 2017 May 1; 47 (5): 653-657.

ObjectiveTo explore the role of Erbin protein and nucleotide-binding oligomerization domain 2/receptor-interacting serine/threonine protein kinases (NOD2/RICK) in GTS-21 activating cholinergic anti-inflammatory pathway.MethodsExperiments were randomly divided into four groups: normal control (NC) group, muramyl dipeptide (MDP) group, 10 μg/mL MDP, GTS-21 (GTS) group, 10 μg/mL MDP plus 50 μg/mL GTS-21 (α7 nAChRs agonist), Erbin shRNA interference (sh-Erbin) group: sh-Erbin RNA plus 10 μg/mL MDP and 50 μg/mL GTS-21. We extract specimens at the point of 1, 6, and 24 h after stimulation of MDP in Raw264.7 macrophages.ResultsAfter stimulation of MDP, the NLR2 mRNA, RICK and Erbin protein, nuclear factor (NF)-κB activity, the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and HMGB1 were significantly increased in MDP group (P <0.05). The expression peak of TNF-α is at 1 h. The peak of HMGB1 is at 24 h. Compared with MDP group, the NLR2 mRNA, RICK, NF-κB, TNF-α, and HMGB1 were significantly decreased, but the Erbin was increased in GTS group (P <0.05). Compared with GTS group, the NLR2 mRNA, RICK, NF-κB, TNF-α, and HMGB1 increase in sh-Erbin group (P <0.05).ConclusionGTS-21 could significantly inhibit MDP-induced pro-inflammatory cytokines responses via activating cholinergic anti-inflammatory pathway, and the Erbin might be the key negative regulatory protein in NLR2/RICK signal transduction.

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