2. Academic Validation
  3. Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity

Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity

  • Mucosal Immunol. 2019 Nov;12(6):1291-1303. doi: 10.1038/s41385-019-0198-5.
Weimin Xu  # 1,  Yuegui Guo  # 1,  Zhenyu Huang  # 1,  Haoxin Zhao 2,  Mingxia Zhou 3,  Yuji Huang 1,  Dongpeng Wen 1,  Jinglue Song 1,  Zhehui Zhu 1,  Mingming Sun 4,  Chen-Ying Liu 1,  Yingwei Chen 3,  Long Cui 1,  Xiaolei Wang 4,  Zhanju Liu 5,  Yili Yang 6,  Peng Du 7
Affiliations

Affiliations

  • 1 Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
  • 2 Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, 215123, China.
  • 3 Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
  • 4 Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
  • 5 Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China. liuzhanju88@126.com.
  • 6 Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, 215123, China. yyl@ism.cams.cn.
  • 7 Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China. dupeng@xinhuamed.com.cn.
  • # Contributed equally.
PMID: 31481750 DOI: 10.1038/s41385-019-0198-5
Abstract

Alpha B-crystallin (CRYAB) is an important member of the small heat shock protein family, and plays a protective and therapeutic role in neurological inflammation. CRYAB expression was assessed in cultured HT29 and Caco-2 cells and inflamed mucosa of patients with inflammatory bowel disease (IBD) and colitis models in mice. Lentivirus-overexpressing and CRSIPR/Cas9 systems were used in different cells to upregulate and silence CRYAB expression, respectively. Cell permeable recombined fusion protein TAT-CRYAB was injected intraperitoneally into dextran sulfate sodium (DSS)- or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice to assess its anti-inflammatory effects. CRYAB was found to be significantly decreased in the inflamed mucosa from IBD patients and DSS-induced colitis in mice, and negatively correlated with the levels of TNF-α and IL-6, respectively. Enforced expression of CRYAB suppressed expression of proinflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, and IL-8) via inhibiting the IKK complex formation, whereas lack of CRYAB expression markedly enhanced proinflammatory responses. Consistently, administration of TAT-CRYAB fusion protein significantly alleviated DSS- or TNBS-induced colitis in mice and protected intestinal barrier integrity. CRYAB regulates inflammatory response in intestinal mucosa by inhibiting IKKβ-mediated signaling and may serve as a novel therapeutic approach in the treatment of IBD.

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