2. Academic Validation
  3. VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages

VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113622. doi: 10.1016/j.intimp.2024.113622.
Jing Zuo 1,  Die Wu 1,  Ying Zhang 2,  Huan Luo 3,  Guoqing Jing 1,  Min Yuan 4,  Qing Fang 1,  Cheng Yang 1,  Xing Wang 1,  Xiaojing Wu 5,  Xuemin Song 6
Affiliations

Affiliations

  • 1 The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Wuchang, 169 Donghu Road, Hubei Province, China.
  • 2 Department of Anesthesiology, Dong Feng Hospital of Hubei Medical University, Shiyan 442000, Zhangwan, 16 Daling Road, Hubei Province, China.
  • 3 Department of Anesthesiology, Cancer Hospital of Chongqing University, Chongqing 400030, Shapingba, 181 Hanyu Road, Chongqing Municipality, China.
  • 4 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Wuchang, 238 Liberation Road, Hubei Province, China.
  • 5 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Wuchang, 238 Liberation Road, Hubei Province, China. Electronic address: RM000851@whu.edu.cn.
  • 6 The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Wuchang, 169 Donghu Road, Hubei Province, China. Electronic address: xueminsong@whu.edu.cn.
PMID: 39550842 DOI: 10.1016/j.intimp.2024.113622
Abstract

Macrophages are present in all tissues and body compartments under homeostatic physiological conditions. Importantly, they play a key role in pathological inflammatory processes when disturbed. They can quickly produce large amounts of inflammatory cytokines in response to danger signals. Macrophages can recognize muramyl dipeptide (MDP) through nucleotide-binding oligomerization domain (NOD)-like receptors, subsequently activating the NF-κB signaling pathway and producing proinflammatory cytokines. Erbin can bind to NOD2 and inhibit MDP-induced NF-κB activation, thus participating in the regulation of inflammatory response. Stabilizing or enhancing Erbin expression is essential for suppressing inflammatory responses. In this study, we used a deubiquitination Enzyme plasmid library to screen for a key Deubiquitinase, VCPIP1, which interacts with Erbin and influences its stability through deubiquitination modification. We investigated whether VCPIP1 affects inflammation using MDP-stimulated RAW 264.7 and BMDMs cells. The results showed that VCPIP1 deficiency reduced Erbin expression and increased NF-κB phosphorylation. Additionally, VCPIP1 deficiency promoted the release of inflammatory factors (IL-1β, IL-6, and TNF-α) in RAW 264.7 cells and BMDMs. This study further expands the role of deubiquitinases (DUBs) in inflammation, providing new insights for the prevention and treatment of sepsis, tumors, immune diseases, and Other inflammatory reactions.

Keywords

Deubiquitination; Erbin; MDP; NF-κB; VCPIP1.

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