Degraded Carrageenan Causing Colitis in Rats Induces TNF Secretion and ICAM-1 Upregulation in Monocytes through NF-κB Activation

Abstract

Carrageenan (CGN) is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN) can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1) to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2) to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule. Peripheral blood monocytes (PBM) and THP-1 monocytic cells were cultured in the presence of either 10 or 40 kDa, dCGN. The 40 kDa, but not the 10 kDa dCGN, induced colitis in in vivo. Degraded CGN inhibited THP-1 cell proliferation in vitro, arresting the cells in G1 phase. In addition, dCGN increased ICAM-1 expression in both PBM and THP-1 cells with a major effect seen after 40 kDa dCGN exposure. Also, dCGN stimulated monocyte aggregation in vitro that was prevented by incubation with anti-ICAM-1 antibody. Finally, dCGN stimulated TNF-α expression and secretion by both PBM and THP-1 cells. All these effects were linked to NF-κB activation. These data strongly suggest that the degraded forms of CGN have a pronounced effect on monocytes, characteristic of an inflammatory phenotype.

κ-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-κB Pathway in HT-29 Cells and AggravatesC.freundii-Induced Inflammation in Mice

“…Previous studies have addressed the ability of carrageenan to increase the proinflammatory cytokines TNF, IL-8, and IL-6 [19, 20, 53]. In our study, IL-6 and TNF were not activated by κ -carrageenan alone but were significantly increased by κ -carrageenan in conjunction with C. freundii .…”

Metabolic effects in mice of cream formulation: Addition of both thickener and emulsifier does not alter lipid metabolism but modulates mucus cells and intestinal endoplasmic reticulum stress

“…No significant differences were observed on Caco-2 permeability and CXCR1 expression (an inflammatory marker) with physiologically degraded κ-CGN (the type of CGN used in the present study) contrary to λ-and ι-CGN that increased these markers (Fahoum et al, 2017). Moreover, a production of tumor necrosis factor α has been observed in human monocyte with degraded ι-CGN, and 5% (wt/vol) of ι-CGN in the drinking water for 55 d causes colitis in rats (Benard et al, 2010). Furthermore, exposure to a small dose of λ-CGN, κ-CGN, and ι-CGN (1 μg/mL) was reported to activate Bcl110 and induces an inflammatory cascade in normal colonic epithelial cells resulting in a production of proinflammatory cytokine IL-8 (Borthakur et al, 2007).…”

“…However, safety of CGN is a topic of intense controversy: a recent review discussed CGN characteristics and digestive fate in this context (David et al, 2018). A degradation product of CGN (namely poligeenan) has been shown to cause gastrointestinal troubles such as colitis and cecal response in rats (Engster and Abraham, 1976;Tobacman, 2001;Benard et al, 2010). Several studies have shown promoting effects of CGN on colon cancer (Watanabe et al, 1978;Arakawa et al, 1986Arakawa et al, , 1988.…”

Clarifying the confusion between poligeenan, degraded carrageenan, and carrageenan: A review of the chemistry, nomenclature, andin vivotoxicology by the oral route

“…The results showed both the higher and lower Mw compounds resulted in substantial lesions and an increase in myeloperoxidase, and infiltration of neutrophils (Benard et al 2010). Benard et al (2010) also assessed the effects of PGN on inflammatory signaling of peripheral blood monocytes (PBMs) in vitro. The authors exposed THP1 (human peripheral blood monocyte) cells to various concentrations, up to 1.0 mg/mL of either 10,000 Da.…”