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Regulation of IL‐1‐induced selective IL‐6 release from human mast cells and inhibition by quercetin
Author(s) -
KandereGrzybowska Kristiana,
Kempuraj Duraisamy,
Cao Jing,
Cetrulo Curtis L,
Theoharides Theoharis C
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706695
Subject(s) - degranulation , signal transduction , protein kinase c , secretion , calphostin c , mast cell , microbiology and biotechnology , biology , cytokine , p38 mitogen activated protein kinases , interleukin 33 , mapk/erk pathway , immunology , interleukin , receptor , biochemistry
1 Mast cells are involved in allergic reactions, but also in innate immunity and inflammation. Crosslinkage of mast cell Fc immunoglobulin E receptors (Fc ɛ RI) by multivalent antigen triggers secretion of granule‐stored mediators, as well as de novo synthesis of cytokines, including interleukin (IL)‐6. 2 We showed recently that the proinflammatory cytokine IL‐1 stimulates human leukemic mast cells (HMC‐1) and human umbilical cord blood‐derived cultured mast cells (hCBMCs) to release newly synthesized IL‐6 without tryptase in the absence of degranulation. 3 Here, we investigated several signal‐transduction pathways activated by IL‐1 leading to IL‐6 production by HMC‐1 and hCBMCs. 4 We also investigated the effect of the flavonol quercetin that was recently shown to strongly inhibit IL‐6 secretion in response to allergic stimulation from hCBMCs. 5 IL‐1 stimulated p38, but did not activate extracellular signal‐regulated kinase (ERK) or c‐jun N‐terminal kinase (JNK); it also did not activate protein kinase C (PKC) isozymes α , β , μ and ζ , except for PKC‐ θ , which was phosphorylated. 6 The p38 inhibitor SB203580 and the PKC inhibitors Calphostin C and Gö6976 completely inhibited IL‐1‐induced IL‐6 production. 7 Quercetin 1–100 μ M inhibited IL‐1‐induced IL‐6 secretion, p38 and PKC‐ θ phosphorylation in a dose‐dependent manner. 8 These results indicate that IL‐1‐stimulated IL‐6 production from human mast cells is regulated by biochemical pathways distinct from IgE‐induced degranulation and that quercetin can block both IL‐6 secretion and two key signal transduction steps involved.British Journal of Pharmacology (2006) 148 , 208–215. doi: 10.1038/sj.bjp.0706695