Hyaluronic acid targets CD44 and inhibits FcepsilonRI signaling involving PKCdelta, Rac1, ROS, and MAPK to exert anti-allergic effect.
Effects of hyaluronic acid (HA) on allergic inflammation were investigated. HA exerted negative effects on beta-hexoaminidase secretion and histamine release in antigen-stimulated rat basophilic leukemia (RBL2H3) cells. HA inhibited interaction between IgE and FcepsilonRI and between FcepsilonRI and PKCdelta. HA inhibited CD44 interaction with PKCalpha, indicating that HA targets CD44. PKCalpha and -delta were responsible for increased Rac1 activity and expression of p47(phox), p67(phox). HA inhibited phosphorylation of PKCalpha and -delta. 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 beta-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 beta-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 FcepsilonRI signaling.
Kim
Youngmi
Y
College of Natural Sciences, Kangwon National University, Chunchon 200-701, Republic of Korea.
Lee
Yun-Sil
YS
Hahn
Jang-Hee
JH
Choe
Jongseon
J
Kwon
Hyung Joo
HJ
Ro
Jai Youl
JY
Jeoung
Dooil
D
D000818:Animals; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D006636:Histamine Release; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000276:immunology / Q000378:metabolism*; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D018925:Chemokines; D018960:Hyaluronan Receptors; D017382:Reactive Oxygen Species; D017455:Receptors, IgE; D007073:Immunoglobulin E; D006820:Hyaluronic Acid; D051745:Protein Kinase C-delta; D020928:Mitogen-Activated Protein Kinases; D001619:beta-N-Acetylhexosaminidases; D020830:rac1 GTP-Binding Protein