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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

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dc.contributor.authorJeong, JS-
dc.contributor.authorKim, HY-
dc.contributor.authorShin, BS-
dc.contributor.authorLee, AR-
dc.contributor.authorYoon, JH-
dc.contributor.authorHahm, TS-
dc.contributor.authorLee, JE-
dc.date.accessioned2019-11-13T00:18:50Z-
dc.date.available2019-11-13T00:18:50Z-
dc.date.issued2018-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/17032-
dc.description.abstractBACKGROUND: 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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dc.language.isoen-
dc.subject.MESHAdaptor Proteins, Signal Transducing-
dc.subject.MESHAnimals-
dc.subject.MESHInterleukin-2-
dc.subject.MESHLigation-
dc.subject.MESHMale-
dc.subject.MESHPeripheral Nervous System Diseases-
dc.subject.MESHPhospholipase C gamma-
dc.subject.MESHProtein Kinase C-theta-
dc.subject.MESHProto-Oncogene Proteins c-cbl-
dc.subject.MESHRats-
dc.subject.MESHSpinal Cord-
dc.subject.MESHSpinal Nerves-
dc.subject.MESHUbiquitin-
dc.subject.MESHUbiquitin-Protein Ligases-
dc.subject.MESHUbiquitination-
dc.subject.MESHZAP-70 Protein-Tyrosine Kinase-
dc.titleIncreased expression of the Cbl family of E3 ubiquitin ligases decreases Interleukin-2 production in a rat model of peripheral neuropathy-
dc.typeArticle-
dc.identifier.pmid30021515-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052554/-
dc.subject.keywordCbl family-
dc.subject.keywordInterleukin-2-
dc.subject.keywordNeuropathic pain-
dc.subject.keywordPhospholipase Cγ1-
dc.subject.keywordUbiquitin-
dc.subject.keywordZAP70-
dc.contributor.affiliatedAuthor김, 하연-
dc.type.localJournal Papers-
dc.identifier.doi10.1186/s12871-018-0555-z-
dc.citation.titleBMC anesthesiology-
dc.citation.volume18-
dc.citation.number1-
dc.citation.date2018-
dc.citation.startPage87-
dc.citation.endPage87-
dc.identifier.bibliographicCitationBMC anesthesiology, 18(1). : 87-87, 2018-
dc.identifier.eissn1471-2253-
dc.relation.journalidJ014712253-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anesthesiology & Pain Medicine
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