TY - JOUR
T1 - Hyaluronic acid targets CD44 and inhibits FcεRI signaling involving PKCδ, Rac1, ROS, and MAPK to exert anti-allergic effect
AU - Kim, Youngmi
AU - Lee, Yun Sil
AU - Hahn, Jang Hee
AU - Choe, Jongseon
AU - Kwon, Hyung Joo
AU - Ro, Jai Youl
AU - Jeoung, Dooil
N1 - 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.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - Anti-allergic effect
KW - CD44
KW - FcεRI
KW - HA
UR - http://www.scopus.com/inward/record.url?scp=40849102303&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2008.01.008
DO - 10.1016/j.molimm.2008.01.008
M3 - Article
C2 - 18289679
AN - SCOPUS:40849102303
SN - 0161-5890
VL - 45
SP - 2537
EP - 2547
JO - Molecular Immunology
JF - Molecular Immunology
IS - 9
ER -