Stimulus-selective regulation of human mast cell gene expression, degranulation and leukotriene production by fluticasone and salmeterol

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DOIResolve DOI: http://doi.org/10.1371/journal.pone.0096891
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TypeArticle
Journal titlePLoS ONE
ISSN1932-6203
Volume9
Issue5
Article numbere96891
Subjectbeta n acetylhexosaminidase; complement component C3a; fluticasone propionate; immunoglobulin E; immunoglobulin E antibody; interleukin 8; leukotriene; monocyte chemotactic protein 1; salmeterol; substance P; tumor necrosis factor; article; cell stimulation; combination chemotherapy; concentration response; controlled study; cytokine production; drug mechanism; drug potentiation; enzyme release; gene expression regulation; human; human cell; incubation time; intracellular signaling; mast cell degranulation; monotherapy
AbstractDespite the fact that glucocorticoids and long acting beta agonists are effective treatments for asthma, their effects on human mast cells (MC) appear to be modest. Although MC are one of the major effector cells in the underlying inflammatory reactions associated with asthma, their regulation by these drugs is not yet fully understood and, in some cases, controversial. Using a human immortalized MC line (LAD2), we studied the effects of fluticasone propionate (FP) and salmeterol (SM), on the release of early and late phase mediators. LAD2 cells were pretreated with FP (100 nM), SM (1 μM), alone and in combination, at various incubation times and subsequently stimulated with agonists substance P, C3a and IgE/anti-IgE. Degranulation was measured by the release of β-hexosaminidase. Cytokine and chemokine expression were measured using quantitative PCR, ELISA and cytometric bead array (CBA) assays. The combination of FP and SM synergistically inhibited degranulation of MC stimulated with substance P (33% inhibition compared to control, n = 3, P< .05). Degranulation was inhibited by FP alone, but not SM, when MC were stimulated with C3a (48% inhibition, n = 3, P<.05). As previously reported, FP and SM did not inhibit degranulation when MC were stimulated with IgE/anti-IgE. FP and SM in combination inhibited substance P-induced release of tumor necrosis factor (TNF), CCL2, and CXCL8 (98%, 99% and 92% inhibition, respectively, n = 4, P<.05). Fluticasone and salmeterol synergistically inhibited mediator production by human MC stimulated with the neuropeptide substance P. This synergistic effect on mast cell signaling may be relevant to the therapeutic benefit of combination therapy in asthma. © 2014 Catalli et al.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); National Institute for Nanotechnology (NINT-INNT)
Peer reviewedYes
NPARC number21272132
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Record identifier22ee7099-98e1-4426-afd7-5ce9910d94c6
Record created2014-07-23
Record modified2016-05-09
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