DJ-X-013 reduces LPS-induced inflammation, modulates Th17/ myeloid-derived suppressor cells, and alters NF-κB expression to ameliorate experimental colitis.

Autor: Mandal M; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Rakib A; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Mamun MAA; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Kumar S; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Park F; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Hwang DJ; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Li W; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Miller DD; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Singh UP; Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: usingh1@uthsc.edu.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Oct; Vol. 179, pp. 117379. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1016/j.biopha.2024.117379
Abstrakt: Scope: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition of unknown etiology, although recent evidence suggests that it is caused by an excessive immune response to mucosal antigens. We determined the anti-inflammatory properties of novel compound DJ-X-013 in vitro in lipopolysaccharide (LPS)-induced macrophages and in an in vivo dextran sodium sulfate (DSS)-induced model of colitis.
Methods and Results: To evaluate the anti-inflammatory properties of DJ-X-013, we used LPS-activated RAW 264.7 macrophages in vitro and a DSS-induced experimental model of colitis in vivo. We examine cellular morphology, and tissue architecture by histology, flow cytometry, RT-qPCR, multiplex, and immunoblot analysis to perform cellular and molecular studies. DJ-X-013 treatment altered cell morphology and expression of inflammatory cytokines in LPS-activated macrophages as compared to cells treated with LPS alone. DJ-X-013 also impeded the migration of RAW 264.7 macrophages by modulating cytoskeletal organization and suppressed the expression of NF-κB and inflammatory markers as compared to LPS alone. DJ-X-013 treatment improved body weight, and colon length and attenuated inflammation in the colon of DSS-induced colitis. Intriguingly, DSS-challenged mice treated with DJ-X-013 induced the numbers of myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), and natural killer T cells (NKT) in the colon lamina propria (LP) relative to DSS. DJ-X-013 also reduced the influx of neutrophils, TNF-α producing macrophages, restricted the number of Th17 cells, and suppressed inflammatory cytokines and NF-κB in the LP relative to DSS.
Conclusion: DJ-X-013 is proposed to be a therapeutic strategy for ameliorating inflammation and experimental colitis.
Competing Interests: Declaration of Competing Interest The authors declare that they do not have any competing interests that might influence this study and have had no involvement with study sponsors.
(Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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