ABSTRACT
Proinflammatory cytokines TNF, IFNG and ILl7 play an important role in eruption of psoriasis. The activation of epidermal keratinocytes with the named cytokines alters their terminal differentiation program and causes their hyperproliferation in the diseased skin. HaCaT cells, which are immortalized human keratinocytes, are often used as a cellular model of psoriasis. The aim of this study was to evaluate changes in gene expression and the proliferation rates in cultured HaCaT cells treated with TNF, IFNG and IL17. We found that HaCaT cells decrease their proliferation rate in response to either IL17 or a combination TNF and IF-NG. The analysis of microarray data discovered a group of 12 genes, which were downregulated in HaCaT after treatments with the named cytokines and upregulated in psoriatic lesional skin. Eight genes were important for DNA replication and they also contributed to two larger networks that regulated cell progression through the cell cycle. We conclude that HaCaT cells have a sufficient limitation as a cellular model of psoriasis due to their treatment with proinflammatory cytokines, namely TNF, IFNG and IL17 does not increase their proliferation rate. Thus, the studies of psoriasis based on HaCaT cells as an experimental model shall take in account this important phenomenon.
Subject(s)
Keratinocytes/metabolism , Psoriasis/genetics , Cell Line , Cell Proliferation , Cells, Cultured , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-17/genetics , Interleukin-17/metabolism , Keratinocytes/physiology , Primary Cell Culture/methods , Psoriasis/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Gene expression analysis for EPHA2 (EPH receptor A2), EPHB2 (EPH receptor B2), S100A9 (S100 calcium binding protein A9), PBEF(nicotinamide phosphoribosyltransferase), LILRB2 (leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 2), PLAUR (plasminogen activator, urokinase receptor), LTB (lymphotoxin beta (TNF superfamily, member 3)), WNT5A (wingless-type MMTV integration site family, member 5A) has been conducted using real-time polymerase chain reaction in specimens affected by psoriasis versus visually intact skin in 18 patients. It was revealed that the expression of the nine examined genes was upregulated in the affected by psoriasis compared to visually intact skin specimens. The highest expression was observed for S100A9, S100AS, PBEF, WNT5A2, and EPHB2 genes. S100A9 and S100A8 gene expression in the affected by psoriasis skin was 100-fold higher versus visually intact skin while PBEF, WNT5A, and EPHB2 gene expression was upregulated more than five-fold. We suggested that the high expression of these genes might be associated with the state of the pathological process in psoriasis. Moreover, the transcriptional activity of these genes might serve a molecular indicator of the efficacy of treatment in psoriasis.
Subject(s)
Gene Expression Profiling/methods , Psoriasis/genetics , Skin/pathology , Adult , Biopsy , Calgranulin A/genetics , Calgranulin B/genetics , Cytokines/genetics , Female , Gene Expression Regulation , Genetic Markers , Humans , Male , Middle Aged , Nicotinamide Phosphoribosyltransferase/genetics , Proto-Oncogene Proteins/genetics , Psoriasis/pathology , Receptor, EphB2/genetics , Wnt Proteins/genetics , Wnt-5a ProteinABSTRACT
Psoriatic and atherosclerotic plaques were examined using the real-time polymerase chain reaction. Expression of the FOSL1 gene proved to substantially increase in both psoriatic lesions of the skin and atherosclerotic lesions of vessels as compared with nonlesion samples.
Subject(s)
Atherosclerosis/genetics , Gene Expression , Proto-Oncogene Proteins c-fos/genetics , Psoriasis/genetics , Adult , Atherosclerosis/pathology , Blood Vessels/metabolism , Blood Vessels/pathology , Humans , Male , Middle Aged , Polymerase Chain Reaction , Psoriasis/pathology , Skin/metabolism , Skin/pathology , Young AdultABSTRACT
Psoriasis was used as a model to analyze the pathogenetic pathways of immune-mediated inflammatory diseases, and the results of bioinformatic, molecular-genetic and proteomic studies are provided. Cell mechanisms, common for the pathogenesis of psoriasis, as well as Crohn's disease, are identified. New approaches for immune-mediated diseases are discussed.
