Effects of Chondroitin Sulfate and Its Oligosaccharides on Toll-Like Receptor-Mediated IL-6 Secretion by Macrophage-Like J774.1 Cells

Abstract

The effects of two types of chondroitin sulphate (CS), CS-A and CS-C, their oligosaccharides (oligo-CSs), and disaccharides (Di-CSs) on toll-like receptor (TLR)-mediated secretion of interleukin (IL)-6 were compared using macrophage-like cell line J774.1. IL-6 secretion in the J774.1 cells was markedly increased by Pam3CS4, LPS, and CpG, the ligands to TLR1/2, 4, and 9 respectively. Among these three ligands, CpG-induced IL-6 was most clearly suppressed by CSs and their digests. Suppression of IL-6 secretion by smaller sized CS-A was stronger than that by intact CS-A, whereas no such size-dependent suppression was apparent for CS-C. Di-4S, the disaccharide unit of the CS-A digest, also showed much stronger suppression than Di-6S, the disaccharide unit of the CS-C digest, and the non-sulfated disaccharide unit, Di-0S. The suppressing activity of oligo-CSs, particularly Di-CSs, against TLR-mediated inflammation was dependent on the CS structure, including the sulfation site.

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

“…On the other hand, considering the influence of the position of a sulfate group in the CS backbone on this GAG‐binding properties, the accessibility of these groups for binding should also be taken into account. It is commonly accepted that in a hydrated environment, the CS chains assume a helical conformation with the 6‐ O ‐sulfated groups that are localized peripherally and the 4‐ O ‐sulfated ones that lie near the midline of the polymer . Thus, the former groups are more accessible to ligands compared to the latter ones.…”

“…By contrast, experiments with a knockout and overexpression of C6ST‐1 revealed that 6‐ O ‐sulfated CS can alleviate a clinical manifestation of the disease . It has also been shown that C‐6‐S inhibited the in vitro secretion of IL‐6 in macrophages, which were proinflammatorily stimulated with CpG via Toll‐like receptor (TLR) 9, more effectively than C‐4‐S . Notably, the impact of CS on macrophage activity can be a crucial issue in the development and progression of a tumor as these cells are responsible for creating and maintaining the protumor–antitumor balance.…”

“…Moreover, chondrocytes that were first treated with C‐6‐S (or C‐4‐S) and then with LPS displayed a significant reduction in the inflammatory response compared to the cells that had only been stimulated with LPS . Additionally, both native CS (especially C‐6‐S) and the CS‐degradation products can effectively inhibit the biological effects that are induced by TLR1/2 and ‐9 . Thus, it is possible that C‐6‐S could directly interact with TLRs in the tumor microenvironment, thereby interfering in the ligand–receptor binding and/or attenuating the signal transduction and downstream signaling.…”

Intestinal microbiology in early life: specific prebiotics can have similar functionalities as human-milk oligosaccharides

“…HMOSs and other NDOSs have been reported to bind to specific receptors on cells of the immune system as summarized by Georgi et al (88) and others (90,(131)(132)(133). Furthermore, in vitro evidence has been obtained for the epithelial transport of HMOSs (131).…”

Oligosaccharides from Palm Kernel Cake Enhances Adherence Inhibition and Intracellular Clearance of Salmonella enterica Serovar Enteritidis In Vitro

“…In order to defend the host against invading pathogens, macrophages possess a broad range of receptors and are able to differentiate self from non-self through the recognition of pathogen-associated molecular patterns [3]. Several of these receptors are known to react to oligosaccharides [54,55]. Studies have also shown that the activation of macrophages may lead to the faster clearance of Salmonella [18,56].…”