Molecular mechanisms of glucocorticoid action in mast cells

Abstract

Glucocorticoids are compounds that have successfully been used over the years in the treatment of inflammatory disorders. They are known to exhibit their effects through the glucocorticoid receptor (GR) that acts to downregulate the action of proinflammatory transcription factors such as AP-1 and NF-κB. The GR also exerts anti-inflammatory effects through activation of distinct genes. In addition to their anti-inflammatory actions, glucocorticoids are also potent antiallergic compounds that are widely used in conditions such as asthma and anaphylaxis. Nevertheless the mechanism of action of this hormone in these disorders is not known. In this article, we have reviewed reports on the effects of glucocorticoids in mast cells, one of the important immune cells in allergy. Building on the knowledge of the molecular action of glucocorticoids and the GR in the treatment of inflammation in other cell types, we have made suggestions as to the likely mechanisms of action of glucocorticoids in mast cells. We have further identified some important questions and research directions that need to be addressed in future studies to improve the treatment of allergic disorders.

Keywords: APC; Allergy; BMMC; DOK 1; DUSP; Doking protein 1; Erk; FITC; GR; GRE; Gab2; Grb2-associated binder 2; IL; IP3; ITAM; IgE; Interleukin; JNK; LAT; MAPK; Mast cells; NTAL; PEP; PI3K; PIP2; PIP3; PLC; PTP; Protein tyrosine phosphatases; SH2 domain containing leukocyte protein of 76kDa; SH2 domain containing polyinositol-5phosphatase 1; SHIP1; SLAP; SLP-76; SYK; Src-like adaptor protein; TNFα; antigen presenting cell; bone marrow derived mast cells; c-Jun N-terminal kinases; dual specificity phosphatase; extracellular regulated kinases; fluorescein isothiocyanate; glucocorticoid receptor; glucocorticoid response elements; immunoglobulin E; immunoreceptor tyrosine based activation motifs; inositol 1,4,5-trisphosphate; linker of activation of T-cells; mitogen-activated protein kinase; non-T-cell activation linker; phosphatidylinositol (3,4,5)-triphosphate; phosphatidylinositol 3-kinase; phosphatidylinositol 4,5-bisphosphate; phospholipase C; proline-, glutamic acid-, serine- and threonine-rich (PEST)-domain enriched tyrosine phosphatase; protein tyrosine phosphatases; spleen tyrosine kinase; tumour necrosis factor.