Hyaluronic acid targets CD44 and inhibits FcRI signaling involving PKCδ, Rac1, ROS, and MAPK to exert anti-allergic effect

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• 作者：Youngmi Kim ; Yun-Sil Lee ; Jang-Hee Hahn ; Jongseon Choe ; Hyung Joo Kwon ; Jai Youl Ro ; Dooil Jeoung
• 关键词：HA ; Anti-allergic effect ; CD44 ; Fc//www.sciencedirect.com/scidirimg/entities/25b.gif" alt="var epsilon" title="var epsilon" border="0">RI
• 刊名：Molecular Immunology
• 出版年：2008
• 期刊代码：112_01615890
• 类别：bio
• 出版时间：May 2008
• 卷：45
• 期：9
• 页码：2537-2547
• 文件大小：1438 K

摘要

Effects of hyaluronic acid (HA) on allergic inflammation were investigated. HA exerted negative effects on β-hexoaminidase secretion and histamine release in antigen-stimulated rat basophilic leukemia (RBL2H3) cells. HA inhibited interaction between IgE and FcRI and between FcRI and PKCδ. HA inhibited CD44 interaction with PKC, indicating that HA targets CD44. PKC and -δ were responsible for increased Rac1 activity and expression of p47^phox, p67^phox. HA inhibited phosphorylation of PKC and -δ. Rac1 was responsible for increased ROS, and NADPH oxidase was the main source for ROS. The inhibition of PKC prevented antigen from increasing phosphorylation of ERK and p38 MAPK. ERK, p38 MAPK, and ROS, were responsible for secretion of β-hexosaminidase, histamine release, and induction of chemokines. HA suppressed induction of chemokines, such as MIP-2 and Sprr-2a. CD44 mediated effect of antigen on phosphorylation of ERK, p38MAPK, ROS production, secretion of β-hexosaminidase, and histamine release. GPCR did not mediate allergic function of antigen or affect anti-allergic function of HA. In vivo anti-allergic effect of HA was investigated using Nc/Nga mice model of DNFB-induced atopic dermatitis. HA reduced skin lesions in Nc/Nga mice treated with DNFB, decreased expression levels of MIP-2, Sprr-2a, and serum IgE level. In conclusion, hyaluronic acid exerts negative effect on allergic inflammation by targeting CD44 and inhibiting FcRI signaling.