title: Alteration in immune responses toward N-deacetylation of hyaluronic acid.
abstract: Hyaluronic acid (HA) is an ubiquitous nonsulfated glycosaminoglycan of the extracellular matrix in all mammalian connective tissues. Along with the age growth, HA will lose its N-acetyl groups in vivo; however, the significance of this physiological process remains largely unknown. Herein, three highly N-deacetylated HAs (dHAs), dHA-5 kDa (Mw: 5 kDa, DD: 100%), dHA-16 kDa (Mw: 16 kDa, DD: 94%) and dHA-110 kDa (Mw: 110 kDa, DD: 72%), were generated after hydrazinolysis. Their capability in the activation of antigen-presenting cells (APCs) was compared with that of their respective HAs. Our results demonstrated that both HAs and dHAs could activate the nuclear factor-kappa B (NF-κB) transcription factor in APCs and induced cytokine production through the Toll-like receptor (TLR)/MyD88 pathway. Notably, the capacity of dHAs in cytokine induction was much lower than that of HAs. In addition, the TLR-2 pathway was much involved following the appearance of zwitterionic motifs in dHAs. Thus, our findings highlight that N-deacetylation renders HA divergences in immune response, which might be implicated in age-induced functional change in endogenous glycosaminoglycans due to the structural modification in vivo.
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Wuxia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Mu
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Dong
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Amin
authors.initials: A
authors.lastname: Zhang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China jduan@nwsuaf.edu.cn.
authors.forename: Jinyou
authors.initials: J
authors.lastname: Duan
mesh_terms: D000107:Acetylation; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D006820:Hyaluronic Acid
keywords: Toll-like receptor; glycosaminoglycan; inflammatory cytokine; zwitterionic polysaccharide