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

Abstract

Background 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 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. Methods IEC lines were treated with caffeine (2.5 mM 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. Results 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 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. Conclusion 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.

Caffeine-Stimulated Intestinal Epithelial Cells Suppress Lipid Accumulation in Adipocytes

“…Orally administered caffeine decreases pro-inflammatory cytokines (TNF-␣ and IL-17F) and increases anti-inflammatory cytokines IL-10 in mouse colons (36). Furthermore, caffeine attenuates acute colitis in a dextran sodium sulfate-induced model of accumulated oxidative stress (36). These results suggest that caffeine decreases gene expression of PAI-1 and IL-8 through suppression of inflammation or oxidative stress in Caco-2 cells.…”

“…Histamine inhibits TNF-␣-and oxidative stress-induced IL-8 secretion in Caco-2 cells (35). Orally administered caffeine decreases pro-inflammatory cytokines (TNF-␣ and IL-17F) and increases anti-inflammatory cytokines IL-10 in mouse colons (36). Furthermore, caffeine attenuates acute colitis in a dextran sodium sulfate-induced model of accumulated oxidative stress (36).…”

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific

“…In contrast, the consumption of tea and coffee which may contain antioxidants and caffeine was associated with a protective effect. Oral caffeine administration has been shown to ameliorate acute colitis in intestinal epithelial cells 27. In addition, green tea polyphenols can improve antioxidants levels and attenuated severity of colitis analogous to sulfasalazine 28…”

Chitinase 3 like 1 suppresses the stability and activity of p53 to promote lung tumorigenesis

“…The extracellular interaction between IL-13Rα2 and Chi3L1 regulates pathogen responses, oxidant injury, inflammation, and melanoma metastasis [39], and also Chi3L1 activates the Wnt/β-catenin, mitogen-activated protein kinase (MAPK), and Protein kinase B (PKB/AKT) signaling pathways via IL-13Rα2 [39] In addition, transmembrane protein 219 (TMEM219), a membrane protein plays a critical role in Chi3L1-induced IL-13Rα2 mediated signaling and responses including oxidant-induced apoptosis, lung injury, and melanoma metastasis [40]. When viewed in combination and based on the previous literatures [39][40][41][43][44][45][46], it is supposed that Chi3L1 is secreted and extracellular Chi3L1 regulates lung metastasis and pathological phenomenon via putative membrane proteins. However, it is still unclear how Chi3L1 accomplishes these varied responses and how Chi3L1 induces lung tumorigenesis.…”