Marine sponge-derived alkaloid ameliorates DSS-induced IBD via inhibiting IL-6 expression through modulating JAK2-STAT3-SOCS3 pathway.
Int Immunopharmacol
; 129: 111576, 2024 Mar 10.
Article
de En
| MEDLINE
| ID: mdl-38350353
ABSTRACT
Cyanogramide (AC14), a novel alkaloid, isolated from the fermentation broth of the marine-derived Actinoalloteichus cyanogriseus. However, the exact role of AC14 in inflammatory bowel disease (IBD) is poorly understood. Our results demonstrated that AC14 exhibited significant inhibition of IL-6 release in THP-1 cells and a "Caco-2/THP-1" coculture system after stimulation with LPS for 24 h. However, no significant effect on TNF-α production was observed. Furthermore, in 2.5 % DSS-induced colitis mice, AC14 treatment led to improvement in body weight, colon length, and intestine mucosal barrier integrity. AC14 also suppressed serum IL-6 production and modulated dysregulated microbiota in the mice. Mechanistically, AC14 was found to inhibit the phosphorylation of Janus kinase (JAK) 2 and signal transducers and activators of transcription (STAT) 3, while simultaneously elevating the expression of suppressor of cytokine signaling (SOCS) 3, both in vivo and in vitro. These findings suggest that AC14 exerts its suppressive effects on IL-6 production in DSS-induced IBD mice through the JAK2-STAT3-SOCS3 signaling pathway. Our study highlights the potential of AC14 as a therapeutic agent for the treatment of IBD.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Porifera
/
Maladies inflammatoires intestinales
/
Alcaloïdes
/
Antinéoplasiques
Limites:
Animals
/
Humans
Langue:
En
Journal:
Int Immunopharmacol
/
Int. immunopharmacol
/
International immunopharmacology
Sujet du journal:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Année:
2024
Type de document:
Article
Pays de publication:
Pays-Bas