Modulation of in vitro Cytokine Release from Human Leukemic Mast Cells (HMC-1) by Glucocorticoids

Abstract

Mast cells are well known effector cells not only in allergic but also in diverse acute and chronic inflammatory diseases. We have shown previously that these cells produce a broad spectrum of cytokines which might contribute to mast cell-dependent pathology. In the present study, we have investigated the influence of four potent glucocorticoids, methylprednisolone-aceponate, methylprednisolone-17-propionate, prednicarbate, and betametasone valerate (10⁵M-10^-9M), on the IL-1Β, IL-3, IL-8, and tumor necrosis factor Α secretion of the HMC-1 mast cell line as measured by ELISA. All four glucocorticoids caused a comparable dose- and time-dependent inhibition of cytokine release from HMC-1 cells stimulated for 24 h with phorbol 12-myristate 13-acetate 25 ng/ml and calcium ionophore 2 × 10^-7M. These results shed further light on the mechanisms involved in antiinflammatory effects of glucocorticoids in allergic inflammation.

Formoterol synergy with des-ciclesonide inhibits IL-4 expression in IgE/antigen-induced mast cells by inhibiting JNK activation

“…Previous studies have demonstrated that glucocorticoids have a potent inhibitory effect on cytokine release in mast cells (Yoshikawa et al, 1999;Lippert et al, 1996;Akabane et al, 2006). However, the inhibitory effect of des-ciclesonide or formoterol on the cytokine release of mast cells is not yet fully understood.…”

“…Our previous studies have demonstrated that the rapid nongenomic effect of GCs functions by preventing the airway constriction reaction and inhibiting degranulation of mast cells in an allergic asthmatic model of guinea pigs (Zhou et al, 2008(Zhou et al, , 2003. In addition, GCs also have a potent inhibitory effect on cytokine release from a human mast cell line (Lippert et al, 1996;Akabane et al, 2006). It has been established that GCs affect β 2 -receptor-mediated signal transduction (Collins et al, 1988); the β 2 -receptor gene is responsive to transcriptional upregulation in response to GC exposure (Baraniuk et al, 1997).…”

Inhibition of cytokine secretion from human leukemic mast cells and basophils by H1‐ and H2‐receptor antagonists

“…Supernatants were examined for their contents of IL-3, 6, 8, TNF-a and GM-CSF by commercially available ELISAs, as described (5,9,10,13,26). For KU812 cells, IL-3 was not studied since basophils fail to produce this cytokine (29).…”

“…Cytokines produced by human mast cells include molecules initiating and boosting TH-2 type immunological reactions as well as a broad spectrum of proinflammatory, growth promoting and chemotactic responses for diverse cell types. These mediators include interleukins (IL)-1, 3,4,5,6,10,13,16, tumor necrosis factor (TNF)-a, granulocyte macrophage colony stimulating factor (GM-CSF), transforming growth factor (TGF)-b, platelet derived growth factor (PDGF), special isoforms of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and the chemokines IL-8, I 309, macrophage chemotactic protein (MCP)-1, ''regulated upon activation normal T cell expressed and secreted'' (RANTES), macrophage inhibitory protein (MIP)-1a, b and lymphotactin (4-7). Human basophils secrete a more restricted cytokine spectrum, with only IL-4, 6, 8, 13 and MIP-1a having been reported so far (8)(9)(10).…”

“…Inhibition of the production and secretion of these mediators is likely to provide a major tool for the treatment of allergic reactions, as supported by the clinical efficacy of agents like corticosteroids and cyclosporin, both well-established inhibitors of cytokine secretion from diverse cell types including mast cells (10)(11)(12)(13)(14). Recently, evidence has emerged that antihistamines can also exert anti-inflammatory effect via this pathway.…”