Glucocorticoids inhibit IL-1beta-induced GM-CSF expression at multiple levels: roles for the ERK pathway and repression by MKP-1

The Biochemical Journal
Robert NewtonM Bergmann

Abstract

In the present study, IL (interleukin)-1beta increased GM-CSF (granulocyte/macrophage colony-stimulating factor) expression from pulmonary A549 cells and primary HBE (human bronchial epithelial) cells. These responses were repressed by the glucocorticoid dexamethasone, allowing the use of A549 cells as a relevant model. IL-1beta induced GM-CSF release into the culture medium by 6 h and in cell lysates (cytosolic) at 2 h. These effects were profoundly inhibited by dexamethasone, yet IL-1beta-induced GM-CSF mRNA and unspliced nRNA (nuclear RNA; a surrogate of transcription rate) were modestly inhibited by dexamethasone at times up to 2 h. Although this indicates an effect on protein synthesis, actinomycin D chase experiments also indicated post-transcriptional repression by dexamethasone. Dexamethasone-dependent mRNA repression increased with time and was prevented by translational blockade. In addition, dexamethasone and the dissociated steroid RU24858 repressed GM-CSF release in an actinomycin D-sensitive manner, thereby implicating glucocorticoid-induced gene expression. At 2 h, IL-1beta-induced expression of GM-CSF protein, but not mRNA, was sensitive to the MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-sign...Continue Reading

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Citations

May 11, 2012·American Journal of Physiology. Renal Physiology·Naomi NiisatoYoshinori Marunaka
Jun 12, 2013·European Journal of Pharmacology·Robert Newton
Sep 27, 2013·High Altitude Medicine & Biology·Kerstin SpliethoffOliver Goetze
Feb 8, 2014·Inhalation Toxicology·Xiaojia WangJared M Brown
May 31, 2011·The Journal of Pharmacology and Experimental Therapeutics·Christopher F RiderRobert Newton
Sep 23, 2010·American Journal of Physiology. Endocrinology and Metabolism·José E Nicoletti-CarvalhoSilvana Bordin
Feb 16, 2019·International Journal of Molecular Sciences·Grace C A ManleyYongliang Zhang

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