Sevoflurane modulates AQPs (1,5) expression and endoplasmic reticulum stress in mice lung with allergic airway inflammation

Abstract

Sevoflurane was found to show protective roles in mice with asthma, however, the mechanism of which needs further exploring. Aquaporins (AQPs) have been demonstrated to be involved in the pathogenesis of asthma, while endoplasmic reticulum stress has been reported to be related to many inflammatory diseases and involved in protein processing, including AQPs. The present study aimed to determine the role of sevoflurane in AQPs (AQP1,3,4,5) expression in mice with allergic airway inflammation and the probable mechanism. The increased number of inflammatory cells infiltrating the lung tissue, and the elevated levels of tumor necrosis factor-α (TNF-α) and interleukin (IL) 13 (IL-13) were all decreased after sevoflurane treatment (all P<0.05). Meanwhile, mRNA levels of AQP1 and AQP5 but not AQP3 and AQP4 were decreased in ovalbumin (OVA)-induced allergic mice lung. Both the decreased mRNA expression and protein levels of AQP1 and AQP5 in allergic lung tissues were reversed by sevoflurane treatment. Furthermore, we established that sevoflurane inhibited the OVA-induced protein increase in the endoplasmic reticulum (ER) stress markers BiP and C/EBP homologous protein (CHOP). Collectively, these findings suggested that sevoflurane modulated the expression and protein level of AOPs (AQP1, AQP5) as well as inhibited ER stress response in OVA-induced allergic airway inflammation of mice.

Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications

“…TGN-020 is a small molecule inhibitor of AQP4 which is being evaluated in several recent studies including lung pathologies [190]. Sevoflurane was shown to modulate expression of AQPs 1 and 5 along with inhibition of ER stress response in OVA-induced allergic airway inflammation [191]. Similar evaluations targeting active components of traditional medicines or known antiinflammatory compounds or repurposing of known drugs have continued in the past decade.…”