E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Power Constriction Harm.
Neurochem Res. 2018 Jun 22;:
Authors: Xue P, Liu X, Shen Y, Ju Y, Lu X, Zhang J, Xu G, Solar Y, Chen J, Gu H, Cui Z, Bao G
E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is related to damaging regulation of receptor tyrosine kinases, sign transduction of antigens and cytokine receptors, and immune response. Nevertheless, the expression and performance of c-cbl within the regulation of neuropathic ache after continual constriction damage (CCI) are unknown. In rat CCI mannequin, c-cbl inhibited the activation of spinal twine microglia and the discharge of pro-inflammatory components together with tumor necrosis issue alpha (TNF-?), interleukin 1 beta (IL-1?) and interleukin 6 (IL-6), which alleviated mechanical and warmth ache by down-regulating extracellular signal-regulated kinase (ERK) pathway. Moreover, exogenous TNF-? inhibited c-cbl protein degree vice versa. Within the main microglia transfected with c-cbl siRNA, when handled with TNF-? or TNF-? inhibitor, the corresponding secretion of IL-1? and IL-6 didn’t change. In abstract, CCI down-regulated c-cbl expression and induced the activation of microglia, then activated microglia launched inflammatory components through ERK signaling to trigger ache. Our information would possibly provide a novel molecular goal for the remedy of CCI-induced neuropathic ache.
PMID: 29934689 [PubMed – as supplied by publisher]