title: Inositol-C2-PAF down-regulates components of the antigen presentation machinery in a 2D-model of epidermal inflammation.
abstract: In cutaneous inflammatory diseases, such as psoriasis, atopic dermatitis and allergic contact dermatitis, skin-infiltrating T lymphocytes and dendritic cells modulate keratinocyte function via the secretion of pro-inflammatory cytokines. Keratinocytes then produce mediators that recruit and activate immune cells and amplify the inflammatory response. These pathophysiological tissue changes are caused by altered gene expression and the proliferation and maturation of dermal and epidermal cells. We recently demonstrated that the glycosidated phospholipid Ino-C2-PAF down-regulates a plethora of gene products associated with innate and acquired immune responses and inflammation in the HaCaT keratinocyte cell line. To further evaluate the influence of Ino-C2-PAF we established an in vitro 2D-model of epidermal inflammation. The induction of inflammation and the impact of Ino-C2-PAF were assessed in this system using a genome-wide microarray analysis. In addition, the expression of selected genes was validated using qRT-PCR and flow cytometry. Treatment of the keratinocytes with a mix of proinflammatory cytokines resulted in transcriptional effects on a variety of genes involved in cutaneous inflammation and immunity, while additional treatment with Ino-C2-PAF counteracted the induction of many of these genes. Remarkably, Ino-C2-PAF suppressed the expression of a group of targets that are implicated in antigen processing and presentation, including MHC molecules. Thus, it is conceivable that Ino-C2-PAF possess therapeutic potential for inflammatory skin disorders, such as psoriasis and allergic contact dermatitis.
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Geo
authors.initials: G
authors.lastname: Semini
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Hildmann
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klein
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Lucka
authors.affiliation: Department of Dermatology, Venerology and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Margarete
authors.initials: M
authors.lastname: Schön
authors.affiliation: Department of Dermatology, Venerology and Allergology, Georg August University, Göttingen, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
authors.affiliation: Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Surganova 13, Minsk 220072, Belarus.
authors.forename: Vadim
authors.initials: V
authors.lastname: Shmanai
authors.affiliation: Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: kerstin.danker@charite.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Danker
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000494:pharmacology; D040081:Protein Array Analysis
chemical_list: C587359:1-O-octadecyl-2-O-(2-inositolylethyl)-glycero-3-phosphatidylcholine; D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D016207:Cytokines; D010972:Platelet Activating Factor; D007294:Inositol
keywords: Alkylphospholipids; Glycosidated phospholipid; Inflammation; Inositol-C2-PAF; Keratinocyte; MHC