Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes

Abstract

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Alginate oligomer induces nitric oxide (NO) production in RAW264.7 cells: elucidation of the underlying intracellular signaling mechanism

“…25) For instance, oligosaccharides of hyaluronan activated dendritic cells via TLR4 to induce TNF-α 19) and they induced inflammation in chondrocytes through TLR4 and CD44 receptors. 21) These findings support the involvement of TLRs in the macrophage-stimulating activities of AOs.…”

“…Similarly, a previous report has suggested that hyaluronan oligosaccharides activate dendritic cells via toll-like receptor (TLR) 4 to induce TNF-α, and the activity of hyaluronan oligosaccharides is greater than that of hyaluronan polysaccharides. 19,21) Thus, oligomerization might represent a promising strategy to increase the bioactivities of these polysaccharides. Previous studies on the structure-activity relationships of AOs have demonstrated that the TNF-α-inducing activities of enzymatically depolymerized AOs in RAW264.7 cells vary with the size and composition of the oligomer.…”

Chemically Modified N-Acylated Hyaluronan Fragments Modulate Proinflammatory Cytokine Production by Stimulated Human Macrophages

“…2 shows the chemical structure of the repeating units of HA and its derivatives. The hydrazinloysis reaction done at 72 h (DHA) generated HA within the molecular mass range that is known to generate an inflammatory response and was therefore used for further studies (9,17,29). In this sample (DHA), the ratio of the integration of the NMR peaks for the three methyl protons in the GlcNAc unit and the anomeric protons of the GlcNAc, GlcUA, and glucosamine was calculated to be 1.24 Ϯ 0.05.…”

“…This suggests that AHA exerts its stimulatory effect on proinflammatory cytokine production by interacting with the TLR-4 cell surface receptor. It has been reported that small molecular mass fragments of HA can exert their inflammatory response either through the TLR-4 receptor or the CD44 cell surface receptor (9,12,17). To determine whether AHA also exerts its inflammatory response through the CD44 cell surface receptor, THP-1 macrophages were treated with AHA with or without the CD44 agonist, HA, or antibodies to CD44.…”

“…In certain pathological conditions such as osteoarthritis and rheumatoid arthritis, HA is degraded into polydisperse lower molecular mass HA (LMHA) by either oxidative hydrolysis or by hyaluronidase-mediated degradation (4,8). Low molecular mass HA binds to certain cell surface receptors such as Toll-like receptors (TLRs) and the cluster of differentiation (CD44) (9 -13) to activate the downstream signaling molecules that stimulate overproduction of proinflammatory cytokines such as TNF-␣, IL-1␤, and IL-6 (9,14). These cytokines induce proteoglycan degradation and matrix metalloproteinase production, leading to further joint destruction.…”