title: Comprehensive assessment of proteins regulated by dexamethasone reveals novel effects in primary human peripheral blood mononuclear cells.
abstract: Inflammation is a physiological process involved in many diseases. Monitoring proteins involved in regulatory effects may help to improve our understanding of inflammation. We have analyzed proteome alterations induced in peripheral blood mononuclear cells (PBMCs) upon inflammatory activation in great detail using high-resolution mass spectrometry. Moreover, the activated cells were treated with dexamethasone to investigate their response to this antiphlogistic drug. From a total of 6886 identified proteins, 469 proteins were significantly regulated upon inflammatory activation. Data are available via ProteomeXchange with identifiers PXD001415-23. Most of these proteins were counter-regulated by dexamethasone, with some exceptions concerning members of the interferon-induced protein family. To confirm some of these results, we performed targeted MRM analyses of selected peptides. The inflammation-induced upregulation of proteins such as IL-1β, IL-6, CXCL2, and GROα was confirmed, however, with strong quantitative interindividual differences. Furthermore, the inability of dexamethasone to downregulate inflammation-induced proteins such as PTX3 and TSG6 was clearly demonstrated. In conclusion, the relation of cell function as well as drug-induced modulation thereof was successfully mapped to proteomes, suggesting targeted analysis as a novel and powerful drug evaluation method. Although most consequences of dexamethasone were found to be compatible with the expected mode of action, some unexpected but significant observations may be related to adverse effects.
authors.affiliation: Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna , Vienna 1090, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bileck
authors.forename: Dominique
authors.initials: D
authors.lastname: Kreutz
authors.forename: Besnik
authors.initials: B
authors.lastname: Muqaku
authors.forename: Astrid
authors.initials: A
authors.lastname: Slany
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D002853:Chromatography, Liquid; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D013058:Mass Spectrometry; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D000683:Serum Amyloid P-Component / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099153:Pentraxins
chemical_list: D000893:Anti-Inflammatory Agents; D002097:C-Reactive Protein; D015815:Cell Adhesion Molecules; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D003907:Dexamethasone; D053583:Interleukin-1beta; D015850:Interleukin-6; D020543:Proteome; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C499706:CXCL2 protein, human; C072273:TNFAIP6 protein, human
keywords: Adverse drug effects; PBMCs; cell biology; drug effects; inflammatory response; mass spectrometry; proteomics; secretome