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

Youngmi Kim, Yun Sil Lee, Jang Hee Hahn, Jongseon Choe, Hyung Joo Kwon, Jai Youl Ro, Dooil Jeoung

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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 FcεRI and between FcεRI and PKCδ. HA inhibited CD44 interaction with PKCα, indicating that HA targets CD44. PKCα and -δ were responsible for increased Rac1 activity and expression of p47phox, p67phox. HA inhibited phosphorylation of PKCα 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 FcεRI signaling.

Original languageEnglish
Pages (from-to)2537-2547
Number of pages11
JournalMolecular Immunology
Volume45
Issue number9
DOIs
StatePublished - May 2008

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Research Foundation and Vascular Research Center, a grant from (A050260) from the Ministry of Health and Welfare of Korea, a grant (FG06-2-23) from the 21C Frontier Functional Human Genome Project from the Ministry of Science & Technology in Korea, and a grant (0307008-1-1) from the Korea Industrial Technology Foundation through the Human Resource Training project for Regional Innovation.

Keywords

  • Anti-allergic effect
  • CD44
  • FcεRI
  • HA

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