A characteristic subset of psoriasis-associated genes is induced by oncostatin-M in reconstituted epidermis.
The pathological manifestations of psoriasis are orchestrated by many secreted proteins, but only a handful, tumor necrosis factor-alpha, IFN-gamma and IL-1, have been studied in great detail. Oncostatin-M (OsM) has also been found in psoriatic skin and we hypothesized that it makes a unique and characteristic contribution to the psoriatic processes. To define in-depth the molecular effects of OsM in epidermis, we used high-density DNA microarrays for transcriptional profiling of OsM-treated human skin equivalents. We identified 374 unambiguously OsM-regulated genes, out of 22,000 probed. OsM suppressed the expression of the "classical" epidermal differentiation markers, but strongly and specifically induced the S100A proteins. Cytoskeletal and complement proteins, proteases, and their inhibitors were also induced by OsM. Interestingly, a large set of genes was induced by OsM at early time points but suppressed later; these genes are known regulatory targets of IFN and thus provide a nexus between the OsM and IFN pathways. OsM induces IL-4 and suppresses the T-helper 1-type and IL-1-responsive signals, potentially attenuating the psoriatic pathology. The data suggest that OsM plays a unique role in psoriasis, different from all other, more thoroughly studied cytokines.
Gazel
Alix
A
Department of Dermatology, New York University School of Medicine, New York, New York 10016, USA.
Rosdy
Martin
M
Bertino
Béatrice
B
Tornier
Carine
C
Sahuc
Florent
F
Blumenberg
Miroslav
M
D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D003165:Complement System Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D053683:Oncostatin M / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics*; D009418:S100 Proteins / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D023822:Tissue Engineering; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D003598:Cytoskeletal Proteins; D011480:Protease Inhibitors; D009418:S100 Proteins; C110294:S100A1 protein; D050791:STAT Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D015847:Interleukin-4; D003165:Complement System Proteins; D010447:Peptide Hydrolases