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- Title
Resveratrol Suppresses Cytokine Production Linked to FcRI-MAPK Activation in IgE-Antigen Complex-Exposed Basophilic Mast Cells and Mice.
- Authors
Han, Seon-Young; Choi, Yean-Jung; Kang, Min-Kyung; Park, Jung Han Yoon; Kang, Young-Hee
- 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 1-25M 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)- 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 (FcRI)-mediated immunoglobulin E (IgE)-antigen complex. The FcRI aggregation was highly enhanced on the surface of mast cells following the HSA stimulation, which was retarded by treatment with 1-25M resveratrol. The IgE-receptor engagement rapidly induced tyrosine phosphorylation of c-Src-related focal adhesion protein paxillin involved in the cytoskeleton rearrangement. The FcRI-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.
- Subjects
ALLERGIES; ANIMAL experimentation; CELL culture; CELLULAR signal transduction; CYTOKINES; DOSE-response relationship in biochemistry; ENZYME-linked immunosorbent assay; IMMUNOHISTOCHEMISTRY; INFLAMMATORY mediators; INTERLEUKINS; MAST cells; MICE; MOLECULAR structure; RESEARCH funding; WESTERN immunoblotting; RESVERATROL; DATA analysis software; DESCRIPTIVE statistics; ONE-way analysis of variance
- Publication
American Journal of Chinese Medicine, 2015, Vol 43, Issue 8, p1605
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X15500913