title: Transcriptome profiling unveils the role of cholesterol in IL-17A signaling in psoriasis.
abstract: Psoriasis is a chronic inflammatory skin disease characterized by altered proliferation and differentiation of keratinocytes as well as infiltration of immune cells. Increased expression of Th17 cells and cytokines secreted by them provides evidence for its central role in the pathogenesis of psoriasis. IL-17A, signature cytokine of Th17 cells was found to be highly differentially expressed in psoriatic lesional skin. However, cellular and molecular mechanism by which IL-17A exerts its function on keratinocyte is incompletely understood. To understand IL-17A mediated signal transduction pathways, gene expression profiling was done and differentially expressed genes were analysed by IPA software. Here, we demonstrate that during IL-17A signaling total cholesterol levels were elevated, which in turn resulted in the suppression of genes of cholesterol and fatty acid biosynthesis. We found that accumulation of cholesterol was essential for IL-17A signaling as reduced total cholesterol levels by methyl β cyclodextrin (MBCD), significantly decreased IL-17A induced secretion of CCL20, IL-8 and S100A7 from the keratinocytes. To our knowledge this study for the first time unveils that high level of intracellular cholesterol plays a crucial role in IL-17A signaling in keratinocytes and may explain the strong association between psoriasis and dyslipidemia.
authors.affiliation: Functional Genomics Unit, CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.|Academy of Scientific &Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Varshney
authors.affiliation: Functional Genomics Unit, CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
authors.forename: Aarti
authors.initials: A
authors.lastname: Narasimhan
authors.forename: Shankila
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Functional Genomics Unit, CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Malik
authors.forename: Kabir
authors.initials: K
authors.lastname: Sardana
authors.affiliation: Functional Genomics Unit, CSIR - Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.|Academy of Scientific &Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Neeru
authors.initials: N
authors.lastname: Saini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000235:genetics; D054418:Chemokine CCL20 / Q000096:biosynthesis; D002648:Child; D002784:Cholesterol / Q000096:biosynthesis / Q000235:genetics*; D050171:Dyslipidemias / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics*; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000008:administration & dosage
chemical_list: D054418:Chemokine CCL20; D005227:Fatty Acids; C508717:IL17A protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol