Dexamethasone rapidly suppresses IL-33-stimulated mast cell function by blocking transcription factor activity

Journal of Leukocyte Biology

Daniel Abebayehu²  Jamie Josephine Avila McLeod²  John J. Ryan²  Gurjas S. Bajaj²  Andrew J. Spence²  Alena P. Chumanevich¹  Oksana Chernushevich²  Anuya Paranjape²  Marcela T. Taruselli²  Bianca Baker²  Carole A. Oskeritzian  and¹  Brian O. Barnstein²  Amina Abdul Qayum² 

[1]  Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA Department of Biology, Virginia Commonwealth University, Richmond, Virginia, USA;Department of Biology, Virginia Commonwealth University, Richmond, Virginia, USA;

关键词: glucocorticoid;    inflammation;    NFκB;    AP-1;    ST2;    neutrophil recruitment;   

DOI  :  10.1189/jlb.3A0316-125R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Mast cells are critical effectors of allergic disease and can be activated by IL-33, a proinflammatory member of the IL-1 cytokine family. IL-33 worsens the pathology of mast cell–mediated diseases, but therapies to antagonize IL-33 are still forthcoming. Because steroids are the mainstay of allergic disease treatment and are well known to suppress mast cell activation by other stimuli, we examined the effects of the steroid dexamethasone on IL-33-mediated mast cell function. We found that dexamethasone potently and rapidly suppressed cytokine production elicited by IL-33 from murine bone marrow–derived and peritoneal mast cells. IL-33 enhances IgE-mediated mast cell cytokine production, an activity that was also antagonized by dexamethasone. These effects were consistent in human mast cells. We additionally observed that IL-33 augmented migration of IgE-sensitized mast cells toward antigen. This enhancing effect was similarly reversed by dexamethasone. Simultaneous addition of dexamethasone with IL-33 had no effect on the phosphorylation of MAP kinases or NFκB p65 subunit; however, dexamethasone antagonized AP-1- and NFκB-mediated transcriptional activity. Intraperitoneal administration of dexamethasone completely abrogated IL-33-mediated peritoneal neutrophil recruitment and prevented plasma IL-6 elevation. These data demonstrate that steroid therapy may be an effective means of antagonizing the effects of IL-33 on mast cells in vitro and in vivo, acting partly by suppressing IL-33-induced NFκB and AP-1 activity.

【 授权许可】

Unknown