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Increased expression of the Cbl family of E3 ubiquitin ligases decreases Interleukin-2 production in a rat model of peripheral neuropathy

Jeong, JS | Kim, HY  | Shin, BS | Lee, AR | Yoon, JH | Hahm, TS | Lee, JE
BMC anesthesiology, 18(1). : 87-87, 2018
Journal Title
BMC anesthesiology
BACKGROUND: Interleukin 2 (IL-2) influences the development and severity of pain due to its antinociceptive and immunomodulatory effects. Its production is influenced by the increased expression of c-Cbl (Casitas B-lineage lymphoma proto-oncogene) and Cbl-b E3 ubiquitin ligases. We evaluated the effects on IL-2-mediated changes in c-Cbl and Cbl-b expression in a rat model of chronic neuropathic pain.
METHODS: Peripheral neuropathy was induced in adult male Sprague-Dawley rats weighing 250-300 g by chronic spinal nerve ligation. Half of the spinal cord ipsilateral to the nerve injury was harvested at 1, 3, and 6 weeks, and the expression levels of IL-2, c-Cbl, Cbl-b, phospholipase C-gamma1 (PLC-gamma1), ZAP70, and protein kinase Ctheta (PKCtheta), as well as ubiquitin conjugation, were evaluated.
RESULTS: Total IL-2 mRNA levels were significantly decreased at 3 and 6 weeks after nerve injury compared to those in sham-operated rats. The mRNA levels of c-Cbl and Cbl-b, as well as the level of ubiquitin conjugation, were significantly increased at 3 and 6 weeks. In contrast, the levels of phosphorylated ZAP70 and PLC-gamma1 were decreased at 3 and 6 weeks after spinal nerve ligation. Ubiquitination of PLC-gamma1 and PKCtheta was increased at 3 and 6 weeks.
CONCLUSIONS: Our results suggest that ubiquitin and the E3 ubiquitin ligases c-Cbl and Cbl-b function as neuroimmune modulators in the subacute phase of neuropathic pain after nerve injury.

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Journal Papers > School of Medicine / Graduate School of Medicine > Anesthesiology & Pain Medicine
Ajou Authors
김, 하연
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