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Indole derivative XCR-5a alleviates LPS-induced inflammation in vitro and in vivo.
- Source :
-
Immunopharmacology & Immunotoxicology . Apr2022, Vol. 44 Issue 2, p157-167. 11p. - Publication Year :
- 2022
-
Abstract
- Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo. This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms. First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1β, IL-6, and TNF-α was determined and H&E staining was performed. Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1β, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway. XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08923973
- Volume :
- 44
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Immunopharmacology & Immunotoxicology
- Publication Type :
- Academic Journal
- Accession number :
- 155832681
- Full Text :
- https://doi.org/10.1080/08923973.2021.2020284