title: Intrinsic alterations of pro-inflammatory mediators in unstimulated and TLR-2 stimulated keratinocytes from atopic dermatitis patients.
abstract: In many patients with atopic dermatitis (AD), the disease is complicated by their enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus (S. aureus). Resistance to bacterial skin infections, e.g. S. aureus, is based on the function of intact innate immune mechanisms in the epidermis, mainly provided by keratinocytes. Toll-like receptor (TLR)-2 recognizes components of S. aureus and is known to be expressed on keratinocytes. The aim of this study was to investigate intrinsic TLR-2 expression and cytokine secretion upon TLR-2 stimulation with peptidoglycan (PGN), lipoteichoic acid (LTA) and N-palmitoyl-S-[2,3-bis(palmitoyl)-(2RS)-propyl]-(R)cysteinyl-alanyl-glycine (Pam3Cys) in keratinocytes from patients with AD compared to healthy controls. Human primary keratinocytes (HPKs) were cultivated from hair follicles of patients with AD and non-atopic healthy controls and stimulated with Pam3Cys, LTA and PGN. TLR-2, TLR-1 and TLR-6 expression were investigated at the mRNA level. IL-6, IL-8, chemokine C-C motif ligand (CCL)-20 and MMP-9 production were studied at the protein level. TLR-2, TLR-1 and TLR-6 were expressed on both HPKs from patients with AD as well as healthy controls without significant differences between these groups. HPKs from patients with AD had an intrinsically reduced capacity to produce IL-6, IL-8, CCL-20 and MMP-9 and responded less to TLR-2 stimulation compared to HPKs from healthy controls. Our findings show evidence for intrinsic alterations in HPKs from patients with AD compared to healthy controls and diminished responses upon TLR-2 stimulation that might contribute to the enhanced susceptibility to skin infections with S. aureus.
authors: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. niebuhr.margarete@mh-hannover.de
authors: Margarete
authors: M
authors: Niebuhr
authors: Annice
authors: A
authors: Heratizadeh
authors: Katja
authors: K
authors: Wichmann
authors: Imke
authors: I
authors: Satzger
authors: Thomas
authors: T
authors: Werfel
mesh_terms: D016022:Case-Control Studies; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013682:Teichoic Acids / Q000494:pharmacology; D051194:Toll-Like Receptor 1 / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000235:genetics
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008074:Lipoproteins; D010457:Peptidoglycan; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D013682:Teichoic Acids; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; C061110:N-palmitoyl-5,6-dipalmitoylcysteinyl-alanyl-glycine; C009900:lipoteichoic acid; D020780:Matrix Metalloproteinase 9