Merck
  • Home
  • Search Results
  • Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells.

Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells.

Journal of gastroenterology (2013-08-09)
In-Ah Lee, Daren Low, Alan Kamba, Victoria Llado, Emiko Mizoguchi
ABSTRACT

The initial trigger of inflammatory bowel disease (IBD) can be partly attributed towards the interaction and invasion of intestinal epithelial cells (IECs) and submucosal compartments. Identifying safe and economical methods to block these interactions may help prevent the onset of early colitis. Chitinase 3-like 1 (CHI3L1) is an inducible host protein that facilitates bacterial attachment and invasion on/into IECs. Therefore, we test the hypothesis of inhibiting CHI3L1 using the pan-chitinase inhibitor caffeine to reduce the likelihood of early colitis onset. IEC lines were treated with caffeine (2.5 or 5 mM) and analyzed for CHI3L1 expression and the impact on bacterial invasion. In vivo, mice were treated with 2.5 mM caffeine and induced with 3.5 % dextran sulfate sodium (DSS)-mediated colitis and subsequently analyzed colitis development. In vitro, caffeine treatment in IEC lines down-regulated CHI3L1 mRNA expression, which resulted in the reduction of bacterial invasion in a caffeine dose-dependent manner. In vivo, mice treated with caffeine displayed a delayed response towards DSS-induced colitis, characterized by lower body weight loss, clinical and histological scores. Bacterial translocation into other organs and pro-inflammatory cytokines production were also reduced in the caffeine-treated mice with DSS-induced colitis. Caffeine treatment also resulted in the loss of CHI3L1-associated AKT signaling pathway activation both in vitro and in vivo. Development of acute colitis is reduced upon caffeine treatment. The mechanism involves the down-regulation of CHI3L1 expression and its associated bacterial interaction effect. Therefore, caffeine is proposed as a safe and economical candidate for successful IBD management.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Caffeine, anhydrous, 99%, FCC, FG
Supelco
Mettler-Toledo Calibration substance ME 18872, Caffeine, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC)
Sigma-Aldrich
Caffeine, anhydrous, tested according to Ph. Eur.
Sigma-Aldrich
Caffeine, powder, ReagentPlus®
Sigma-Aldrich
Caffeine, BioXtra
Sigma-Aldrich
Caffeine, Sigma Reference Standard, vial of 250 mg
Sigma-Aldrich
Caffeine, meets USP testing specifications, anhydrous
Supelco
Caffeine Melting Point Standard, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Caffeine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Caffeine, European Pharmacopoeia (EP) Reference Standard
USP
Methyl alcohol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Human IL-4 ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Mouse IL-4 ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Mouse IL-4 ELISA Kit, for cell and tissue lysates
Supelco
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 5 mm × 8 in.
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Supelco
Caffeine, certified reference material, TraceCERT®
USP
Caffeine melting point standard, United States Pharmacopeia (USP) Reference Standard
Supelco
Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%
USP
Caffeine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Cotton Rat IL4 / Interleukin 4 ELISA Kit
Supelco
Methanol, analytical standard
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, NMR reference standard
Supelco
Melting point standard 235-237°C, analytical standard
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Caffeine for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)