Increased expression of the Cbl family of E3 ubiquitin ligases decreases Interleukin-2 production in a rat model of peripheral neuropathy
- Authors
- Jeong, Ji Seon; Kim, Ha Yeon; Shin, Byung Seop; Lee, Ae Ryoung; Yoon, Ji Hyun; Hahm, Tae Soo; Lee, Ja Eun
- Issue Date
- 18-Jul-2018
- Publisher
- BMC
- Keywords
- Cbl family; Interleukin-2; Neuropathic pain; Phospholipase C gamma 1; Ubiquitin; ZAP70
- Citation
- BMC ANESTHESIOLOGY, v.18, no.1
- Journal Title
- BMC ANESTHESIOLOGY
- Volume
- 18
- Number
- 1
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/45226
- DOI
- 10.1186/s12871-018-0555-z
- ISSN
- 1471-2253
- Abstract
- 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-, c-Cbl, Cbl-b, phospholipase C-gamma 1 (PLC-gamma 1), ZAP70, and protein kinase C theta (PKC theta), 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-gamma 1 were decreased at 3 and 6 weeks after spinal nerve ligation. Ubiquitination of PLC-gamma 1 and PKC theta 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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Collections - College of Natural Sciences > Department of Life Science > 1. Journal Articles
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