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Neurochem Res. 2018 Aug;43(8):1631-1640. doi: 10.1007/s11064-018-2578-8. Epub 2018 Jun 22.

E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury.

Author information

1
Department of Spine Surgery, the Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
2
Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu, China.
3
Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
4
Medical College, Nantong University, Nantong, 226001, Jiangsu, China.
5
Department of Spine Surgery, the Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. zhimingcui@126.com.
6
Department of Spine Surgery, the Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. baoguofeng2018@sina.com.

Abstract

E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway. Additionally, exogenous TNF-α inhibited c-cbl protein level vice versa. In the primary microglia transfected with c-cbl siRNA, when treated with TNF-α or TNF-α inhibitor, the corresponding secretion of IL-1β and IL-6 did not change. In summary, CCI down-regulated c-cbl expression and induced the activation of microglia, then activated microglia released inflammatory factors via ERK signaling to cause pain. Our data might supply a novel molecular target for the therapy of CCI-induced neuropathic pain.

KEYWORDS:

Chronic constriction injury (CCI); Extracellular signal-regulated kinase (ERK); Inflammatory factors; Microglia; c-Caritas B cell lymphoma (c-cbl)

PMID:
29934689
DOI:
10.1007/s11064-018-2578-8
[Indexed for MEDLINE]

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