MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/x01/MSV000079944/primary200OK0000ProteomicsDr Christopher GernerQ ExactiveHomo Sapiens (ncbitaxon:9606)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=a15f734d4a264c4eb501693dca9acd5fMassIVE44UNIMOD:4 - "Iodoacetamide derivative."UNIMOD:1 - "Acetylation."UNIMOD:35 - "Oxidation or Hydroxylation."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.Comprehensive assessment of proteins regulated by dexamethasone reveals novel effects in primary human peripheral blood mononuclear cells.Bileck Andrea A, Kreutz Dominique D, Muqaku Besnik B, Slany Astrid A, Gerner Christopher COradexon, Auxiron, Azium, Leukocyte, human being, 9-fluoro-11, Peripheral Blood Mononuclear Cells, Modern, Proteins, dexametasona, Dexacortin, Dexpak, Gene, PBMC Peripheral Blood Mononuclear Cells, Hexadecadrol, 16alpha)-9-fluoro-11, Human, Mononuclear Leukocyte., 17, Zema-Pak, Homo sapiens, Dexasone, Protein, Dexacortal, Gene Products, Millicorten, Peripheral Blood Mononuclear Cell, Decaject, Decadron, Solurex, fluormethylprednisolone, 1-dehydro-16alpha-methyl-9alpha-fluorohydrocortisone, dexamethasonum, Man, 16alpha-methyl-9alpha-fluoro-1-dehydrocortisol, Aeroseb-Dex, Decaject-L.A., Maxidex, 9alpha-fluoro-16alpha-methylprednisolone, Dexason, Peripheral Blood Human Mononuclear Cells, Hexadrol, 16alpha)-, Pregna-1, 21-trihydroxy-16-methylpregna-1, Man (Taxonomy), Corson, Cortisumman, Ozurdex, (11beta, 20-dione, Decaspray, Decameth, human, 4-diene-3, Decalix, Protein Gene Products, dexamethasone, Gene Proteins, Mononuclear, Diodex, 21-trihydroxy-16-methyl-, Mononuclear Leukocytes, Calonat, Modern Man, Decaject L.A., DexPak, Methylfluorprednisolone, Decacort, humansDifferentiation-Inducing Protein, Networks, Oradexon, Myeloid Differentiation-Inducing Protein, B-Cell Stimulatory Factor-2, CDF, Azium, Inflammations, 9-fluoro-11, Kinship, single-organism process, Product, Peripheral Blood Mononuclear Cells, determination, Myeloid, Il-6, Hepatocyte-Stimulating Factor, protein, Mgsa-b, Evaluation Studies, BEST:LD15161, B-cell stimulatory factor 2, DGro, Physiological Concepts, B Cell, Drug Evaluation Study, Polypeptides, B Cell Stimulatory Factor 2, Readability, protein polypeptide chains, Techniques, 17, peptido, diseases, ak, Method, Pharmaceutical Product, IL-6, Interferon beta-2, AI607804, Concepts, 1, Life Cycle, Hybridoma growth factor, 2, diseases and disorders, Peripheral Blood Mononuclear Cell, Analysis, protein aggregate, Phenomenon, 16alpha-methyl-9alpha-fluoro-1-dehydrocortisol, INSL3R, Family Life Cycle, GROb, Mass Spectrum Analysis, 3-Propanetriol, Dexason, strong, human disease, Oelsuess, Drug Evaluation, inflammatory response, 21-trihydroxy-16-methylpregna-1, Kinship Network, peptides, MGSA-b, Analyses, (11beta, Physiological Concept, Decaspray, m9-m10, Decameth, E(spl)gro, proteins, dAES2, dAES1, MIP2, Mip2, Decalix, B Cell Differentiation Factor 2, TSG-14, GREAT, Phenomenas, interleukin-6 receptor ligand, Mononuclear, Methodological Studies, Mononuclear Leukocytes, medicine, Pharmaceutical, physiological process, Groucho, Great, Homo sapiens disease, Methylfluorprednisolone, Family Life Cycles, Physiological, Glyceritol, 3-dihydroxypropionic acid, Physiological Process, MIP-2, Process, dexametasona, Dexpak, Up-Regulation (Physiology), B Cell Stimulatory Factor-2, beta-2, single organism process, Procedure, PBMC Peripheral Blood Mononuclear Cells, HSF, Spectrum Analysis, 16alpha)-9-fluoro-11, results, Multiple Reaction Monitoring, Spectroscopy, Evaluation, BSF2, Interferon beta 2, Zema-Pak, glycerol, Diseases, Dexacortal, Millicorten, Pharmaceutic, Physiological Phenomenon, Differentiation Factor-2, fluormethylprednisolone, Filiation, activation, Decaject-L.A., 9alpha-fluoro-16alpha-methylprednisolone, LGR8, Hexadrol, Differentiation Factor 2, Lgr8, Gro, GRO, mIL-1b, Drug Evaluation Studies, Corson, glycerine, Upregulation, Cortisumman, Ozurdex, 20-dione, Spectrometry, Methodological, Plasmacytoma, Methodological Study, 4-diene-3, Grg/TLE, side effects., Life Cycles, disease, IFNB2, gro, 21-trihydroxy-16-methyl-, Plasmacytoma Growth Factor, Calonat, Decaject L.A., DexPak, Polypeptide, Innate, Physiological Processes, Interferon, Proteomes, Inflammatory Response, other disease, Family Member, Procedures, Processes, E(spl)-WD, Evaluation Study, B-cell hybridoma growth factor, number, m9/m10, Gene, B-Cell, BcDNA.LD33829, Network, B-Cell Differentiation Factor, anon-WO0118547.385, Spectrum Analyses, Scyb1, Scyb2, protein-containing complex, Hexadecadrol, presence, Fsp, method, glycyl alcohol, HGF, MIP-2a, Propanetriol, polypeptide chain, resilient, Evaluations, Il-1b, tough, method used in an experiment, Hepatocyte Stimulating Factor, Trihydroxypropane, Gene Products, Mass, Studies, disease or disorder, Growth Factor, Decaject, Decadron, CTL differentiation factor, Technique, Mass Spectroscopy, Aeroseb-Dex, Drugs, 16alpha)-, Gpr106, Differentiation Factor, SCYB2, MRM, En-spl, Research, Drug Evaluations, Receptor Up-Regulation, IL-1beta, m10, Hybridoma Growth Factor, Up Regulation, Interleukin 6, Glycerin, inflammation, RXFPR2, l(3)gro, ASMD, KC, Scyb, DmelCG8384, non-neoplastic, Study, E(spl)m9/m10, drugs, glycerolum, Diodex, Innate Inflammatory Response, Mononuclear Leukocyte, BcDNA:LD33829, N51, m9, disorder, IL6, peptidos, Preparation, Kinship Networks, Family, GPR106, Pharmaceuticals, Products, Auxiron, Leukocyte, Family Research, MGI-2, protein complex, Glyzerin, drug, Proteins, disorders, Dexacortin, total expressed protein, medical condition, Myeloid Differentiation Inducing Protein, ASOD, Cell, Peptide, Concept, Family Members, count in organism, MS, native protein, natural protein, Dexasone, Mgsa, IFN-beta-2, Protein, chemical analysis, Phenomena, condition, BSF-2, Solurex, m9/10, 1-dehydro-16alpha-methyl-9alpha-fluorohydrocortisone, biological process, dexamethasonum, E(spl)[2], Mass Spectrum Analyses, Maxidex, B-Cell Differentiation Factor-2, Peripheral Blood Human Mononuclear Cells, Mass Spectrum, IFN-beta 2, BEST:GM01575, 3-Trihydroxypropane, Pregna-1, Pharmaceutic Preparations, CG8384, Gro1, dGro, GRO2, Gro2, Interleukin HP-1, Understanding, LGR8.1, CINC-2a, MIP2A, Protein Gene Products, dexamethasone, Drug, plan specification, Gene Proteins, Preparations, B Cell Differentiation Factor, Hybridoma, CTRCT11, Families, Innate Inflammatory Responses, B-Cell Stimulatory Factor 2, Peptid, CTPP4, assay, Decacort, Pharmaceutical Products, Ptx3, Relatives, PTX3, Pharmaceutical PreparationOradexon, Auxiron, Azium, Leukocyte, human being, 9-fluoro-11, Peripheral Blood Mononuclear Cells, Modern, Proteins, dexametasona, Dexacortin, Dexpak, Gene, PBMC Peripheral Blood Mononuclear Cells, Hexadecadrol, 16alpha)-9-fluoro-11, Human, 17, Zema-Pak, Homo sapiens, Dexasone, Protein, Dexacortal, Gene Products, Millicorten, Cell., Peripheral Blood Mononuclear Cell, Decaject, Decadron, Solurex, fluormethylprednisolone, 1-dehydro-16alpha-methyl-9alpha-fluorohydrocortisone, dexamethasonum, Man, 16alpha-methyl-9alpha-fluoro-1-dehydrocortisol, Aeroseb-Dex, Decaject-L.A., Maxidex, 9alpha-fluoro-16alpha-methylprednisolone, Dexason, Peripheral Blood Human Mononuclear Cells, Hexadrol, 16alpha)-, Pregna-1, 21-trihydroxy-16-methylpregna-1, Man (Taxonomy), Corson, Cortisumman, Ozurdex, (11beta, 20-dione, Decaspray, Decameth, human, 4-diene-3, Decalix, Protein Gene Products, dexamethasone, Gene Proteins, Mononuclear, Diodex, 21-trihydroxy-16-methyl-, Mononuclear Leukocytes, Mononuclear Leukocyte, Calonat, Modern Man, Decaject L.A., DexPak, Methylfluorprednisolone, Decacort, humansDifferentiation-Inducing Protein, Networks, Oradexon, Myeloid Differentiation-Inducing Protein, B-Cell Stimulatory Factor-2, CDF, Azium, Inflammations, 9-fluoro-11, Kinship, single-organism process, Product, Peripheral Blood Mononuclear Cells, determination, Myeloid, Il-6, Hepatocyte-Stimulating Factor, protein, Mgsa-b, Evaluation Studies, B-cell stimulatory factor 2, Physiological Concepts, B Cell, Drug Evaluation Study, Polypeptides, B Cell Stimulatory Factor 2, Readability, protein polypeptide chains, Techniques, 17, peptido, diseases, ak, Method, Pharmaceutical Product, IL-6, Interferon beta-2, AI607804, Concepts, Life Cycle, Hybridoma growth factor, diseases and disorders, Peripheral Blood Mononuclear Cell, Analysis, protein aggregate, Phenomenon, 16alpha-methyl-9alpha-fluoro-1-dehydrocortisol, INSL3R, Family Life Cycle, GROb, Mass Spectrum Analysis, Dexason, strong, human disease, Drug Evaluation, inflammatory response, 21-trihydroxy-16-methylpregna-1, Kinship Network, peptides, MGSA-b, Analyses, (11beta, Physiological Concept, Decaspray, Decameth, proteins, MIP2, Mip2, Decalix, B Cell Differentiation Factor 2, TSG-14, GREAT, Phenomenas, interleukin-6 receptor ligand, Mononuclear, Methodological Studies, Mononuclear Leukocytes, medicine, Pharmaceutical, physiological process, Great, Homo sapiens disease, Methylfluorprednisolone, Family Life Cycles, Physiological, Physiological Process, MIP-2, Process, dexametasona, Dexpak, B Cell Stimulatory Factor-2, beta-2, single organism process, Procedure, PBMC Peripheral Blood Mononuclear Cells, HSF, Spectrum Analysis, 16alpha)-9-fluoro-11, results, Multiple Reaction Monitoring, Spectroscopy, Evaluation, BSF2, Interferon beta 2, Zema-Pak, Diseases, Dexacortal, Millicorten, Pharmaceutic, Physiological Phenomenon, Differentiation Factor-2, fluormethylprednisolone, Filiation, activation, Decaject-L.A., 9alpha-fluoro-16alpha-methylprednisolone, LGR8, Hexadrol, Differentiation Factor 2, Lgr8, Drug Evaluation Studies, Corson, Cortisumman, Ozurdex, 20-dione, Spectrometry, Methodological, Plasmacytoma, Methodological Study, 4-diene-3, side effects., Life Cycles, disease, IFNB2, 21-trihydroxy-16-methyl-, Plasmacytoma Growth Factor, Calonat, Decaject L.A., DexPak, Polypeptide, Innate, Physiological Processes, Interferon, Proteomes, Inflammatory Response, other disease, Family Member, Procedures, Processes, Evaluation Study, B-cell hybridoma growth factor, number, Gene, B-Cell, Network, B-Cell Differentiation Factor, Spectrum Analyses, Scyb2, protein-containing complex, Hexadecadrol, presence, method, HGF, MIP-2a, polypeptide chain, resilient, Evaluations, tough, method used in an experiment, Hepatocyte Stimulating Factor, Gene Products, Mass, Studies, disease or disorder, Growth Factor, Decaject, Decadron, CTL differentiation factor, Technique, Mass Spectroscopy, Aeroseb-Dex, Drugs, 16alpha)-, Gpr106, Differentiation Factor, SCYB2, MRM, Research, Drug Evaluations, Hybridoma Growth Factor, Interleukin 6, inflammation, RXFPR2, ASMD, Scyb, non-neoplastic, Study, drugs, Diodex, Innate Inflammatory Response, Mononuclear Leukocyte, disorder, IL6, peptidos, Preparation, Kinship Networks, Family, GPR106, Pharmaceuticals, Products, Auxiron, Leukocyte, Family Research, MGI-2, protein complex, drug, Proteins, disorders, Dexacortin, total expressed protein, medical condition, Myeloid Differentiation Inducing Protein, ASOD, Cell, Peptide, Concept, Family Members, count in organism, MS, native protein, natural protein, Dexasone, IFN-beta-2, Protein, chemical analysis, Phenomena, condition, BSF-2, Solurex, 1-dehydro-16alpha-methyl-9alpha-fluorohydrocortisone, biological process, dexamethasonum, Mass Spectrum Analyses, Maxidex, B-Cell Differentiation Factor-2, Peripheral Blood Human Mononuclear Cells, Mass Spectrum, IFN-beta 2, Pregna-1, Pharmaceutic Preparations, GRO2, Gro2, Interleukin HP-1, Understanding, LGR8.1, CINC-2a, MIP2A, Protein Gene Products, dexamethasone, Drug, plan specification, Gene Proteins, Preparations, B Cell Differentiation Factor, Hybridoma, CTRCT11, Families, Innate Inflammatory Responses, B-Cell Stimulatory Factor 2, Peptid, CTPP4, assay, Decacort, Pharmaceutical Products, Ptx3, Relatives, PTX3, Pharmaceutical Preparation0PXD001419trueComprehensive Assessment of Proteins Regulated by Dexamethasone Reveals Novel Effects in Primary Human Peripheral Blood Mononuclear Cells - cytoplasmic proteins of inflammatory stimulated cellsInflammation 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. 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 up-regulation of proteins such as IL-1beta, IL-6, CXCL2 and GROα was confirmed, however with strong quantitative inter-individual differences. Furthermore, the inability of dexamethasone to down-regulate 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. While most consequences of dexamethasone were found compatible with the expected way of action, some unexpected but significant observations may relate with adverse effects.Wed Jul 20 07:23:00 BST 2016MSV00007994425347463