Mesalazine Activates Adenosine Monophosphate-activated Protein Kinase: Implication in the Anti-inflammatory Activity of this Anti-colitic Drug / Heejung Park, Wooseong Kim, Dayoon Kim, Seongkeun Jeong, Yunjin Jung

Objective: Mesalazine, 5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug that is most widely used for the treatment of Inflammatory Bowel Disease (IBD). Despite extensive clinical use, the exact pharmacological mechanism underlying the anti-colitic effects of 5-ASA has not yet been elucidated. A potential molecular mechanism underlying 5-ASA-mediated anti-colitic activity was investigated. Methods: An anti-inflammatory pharmacology of 5-ASA was scrutinized in human colon carcinoma cells and murine macrophages and in a TNBS-induced rat colitis model. Results: 5-ASA induced phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrate acetyl-CoA carboxylase in cells. 5-ASA activation of AMPK occurred regardless of the presence of the pro-inflammatory mediators, Tumor Necrosis Factor Alpha (TNF-α) and lipopolysaccharide. 5-ASA inhibits TNF-α-dependent Nuclear Factor-Kappa B (NF-κB) activation, which was dampened by AMPK inhibition. Oral gavage of sulfasalazine (a colon-specific prodrug of 5- ASA) or rectal administration of 5-ASA ameliorated 2,4,6-trinitrobenzene sulfonic acid (TNBS)- induced rat colitis and activated AMPK in the inflamed colonic tissues while markedly diminishing the levels of NF-κB-regulated pro-inflammatory mediators cyclooxygenase-2, inducible nitric oxide synthase, and cytokine-induced neutrophil chemoattractant-3, elevated by the induction of inflammation. Rectal co-administration of 5-ASA and an AMPK inhibitor undermined 5-ASA-mediated activation of AMPK and its anti-colitic effects. Conclusion: These findings suggest that the activation of AMPK is involved in 5-ASA-mediated anticolitic effects at least partly via interference with pro-inflammatory NF-κB signaling.

Medienart:	E-Artikel

Erscheinungsjahr:	2019
Erschienen:	2019

Enthalten in:	Zur Gesamtaufnahme - volume:12
Enthalten in:	Current molecular pharmacology - 12(2019), 4, Seite 272-

Sprache:	Englisch

Beteiligte Personen:	Park, HeejungHeejung [VerfasserIn] Kim, Wooseong [VerfasserIn] Kim, Dayoon [VerfasserIn] Jeong, Seongkeun [VerfasserIn] Jung, Yunjin [VerfasserIn]

Links:	FID Access [lizenzpflichtig]

Umfang:	1 Online-Ressource (9 p)

Förderinstitution / Projekttitel:

PPN (Katalog-ID):	KFL001024175