Dexmedetomidine promotes inflammation resolving through TGF-β1 secreted by F4/80+Ly6G+ macrophage

Autor: Ji Xiao, Lin-Chao Li, Fang Gao-Smith, Shengwei Jin, Jin-Ni Wu, Yan Chen, Pu-Hong Zhang, Yi Yang, Yang Tian, Jianguang Wang
Rok vydání: 2021
Předmět:
Zdroj: International Immunopharmacology. 95:107480
ISSN: 1567-5769
DOI: 10.1016/j.intimp.2021.107480
Popis: Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist, which can regulate inflammatory responses. However, whether DEX interferes with the inflammation resolving remains unclear. Here, we reported the effects of DEX on zymosan-induced generalized inflammation in mice during resolution. Mice were administered intraperitoneally with DEX after the initiation of sepsis. The resolution interval (Ri), a vital resolution indice, decreased from twelve hours to eight hours after the administration of DEX. The induction of peritoneal pro-inflammatory interleukin [IL] - 1β and tumour necrosis factor-α (TNF-α) appeared to be inhibited. Of interest, the anti-inflammatory transforming growth factor-β1 (TGF-β1) but not IL-10 levels were up-regulated at twenty-four hours in the DEX group along with 1.0 mg/mice zymosan A (ZyA) treatment. The expression levels of multiple genes related to protective immune processes and clearance functions were detected and revealed the same trends. DEX markedly increased the F4/80+Ly6G+ macrophage population. Additionally, the adequate apoptotic neutrophil clearance from injury after DEX installation could be reverse by opsonization or co-instillation of TGF-β1 neutralizing antibody in vivo, promoting the inflammation-resolution programs. In conclusion, DEX post-treatment, via the increase of F4/80+Ly6G+ macrophages, provokes further secretion of TGF-β1, leading to the attenuated cytokine storm and accelerated inflammation resolving.
Databáze: OpenAIRE
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