title: Resveratrol Suppresses Cytokine  Production Linked to FcεRI-MAPK  Activation in IgE-Antigen Complex-Exposed  Basophilic Mast Cells and Mice.
abstract: A complicated interplay between resident mast cells and other recruited inflammatory cells contributes to the development and progression of allergic inflammation entailing the promotion of T helper 2 (Th2) cytokine responses. The current study examined whether resveratrol suppressed the production of inflammatory Th2 cytokines in cultured rat basophilic leukemia RBL-2H3 cells. Cells pre-treated with resveratrol nontoxic at 1–25 μM were sensitized with anti-dinitrophenyl (anti-DNP), and subsequently stimulated by dinitrophenyl-human serum albumin (DNP–HSA) antigen. Resveratrol dose-dependently diminished the secretion of interleukin (IL)-3, IL-4, IL-13 as well as tumor necrosis factor (TNF)-α by the antigen stimulation from sensitized cells. It was found that resveratrol mitigated the phosphorylation of p38 MAPK, ERK, and JNK elevated in mast cells exposed to Fc epsilon receptor I (FcεRI)-mediated immunoglobulin E (IgE)-antigen complex. The FcεRI aggregation was highly enhanced on the surface of mast cells following the HSA stimulation, which was retarded by treatment with 1–25 μM resveratrol. The IgE-receptor engagement rapidly induced tyrosine phosphorylation of c-Src-related focal adhesion protein paxillin involved in the cytoskeleton rearrangement. The FcεRI-mediated rapid activation of c-Src and paxillin was attenuated in a dose-dependent manner. In addition, the paxillin activation entailed p38 MAPK and ERK-responsive signaling, but the JNK activation was less involved. Consistently, oral administration of resveratrol reduced the tissue level of phosphorylated paxillin in the dorsal skin of DNP–HSA-challenged mice. The other tyrosine kinase Tyk2-STAT1 signaling was activated in the dorsal epidermis of antigen-exposed mice, which was associated with allergic inflammation. These results showed that resveratrol inhibited Th2 cytokines- and paxillin-linked allergic responses dependent upon MAPK signaling. Therefore, resveratrol may possess the therapeutic potential of targeting mast cells in preventing the development of allergic inflammation.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Han
authors.forename: Yean-Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kang
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004140:Dinitrophenols / Q000276:immunology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D017455:Receptors, IgE / Q000276:immunology*; D000077185:Resveratrol; D012709:Serum Albumin / Q000276:immunology*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D004140:Dinitrophenols; D017455:Receptors, IgE; D012709:Serum Albumin; D013267:Stilbenes; C058064:dinitrophenyl-human serum albumin conjugate; D007073:Immunoglobulin E; D000077185:Resveratrol