Abstract

IntroductionAsthma–chronic obstructive pulmonary (COPD) overlap (ACO) coexists with asthma and COPD syndrome characteristics, with more frequent exacerbations, heavier disease burden, higher medical utilization, and even lower quality of life. However, the ACO standard medications supported by evidence-based medicine have not yet appeared.MethodsBy using an ACO mouse model established previously and LPS-stimulated RAW264.7 macrophages in vitro, a potential therapeutic candidate, EAPP-2, was screened from derivatives of 3-arylbenzofuran, and its effect and mechanism on ACO inflammation were evaluated.ResultsEAPP-2 significantly alleviated airway inflammation in ACO mice and also inhibited the inflammatory reactions in LPS-induced RAW264.7 macrophages in vitro. Furthermore, EAPP-2 significantly inhibited the expression and phosphorylation of spleen tyrosine kinase (Syk), a common target regulating both eosinophils and neutrophils inflammation. In addition to this, EAPP-2 significantly down-regulates the expression of NF-κB, p-NF-κB, and NLRP3 in vivo and in vitro. Moreover, by using specific inhibitors in vitro, it was validated that EAPP-2 targeted on Syk and then regulated its downstream NF-κB and NLRP3.ConclusionEAPP-2 is shown to be a potentially useful therapeutic candidate for ACO, and its mechanism is at least partially achieved by targeting on Syk and then inhibiting NF-κB or NLRP3. Moreover, this study suggests that Syk may be a potentially effective target for ACO therapy.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.