title: CCL7 contributes to the TNF-alpha-dependent inflammation of lesional psoriatic skin.
abstract: Chemokines are small chemotactic proteins that have a crucial role in leukocyte recruitment into tissue. Targeting these mediators has been suggested as a potential therapeutic option in inflammatory skin diseases such as psoriasis. Using quantitative RT-PCR, we found CCL7, a chemokine ligand known to interact with multiple C-C chemokine receptors, to be markedly increased in lesional psoriasis as opposed to atopic dermatitis, lichen planus, non-lesional psoriatic and normal control skin. Surprisingly, this increase in CCL7 mRNA expression exceeded that of all other chemokines investigated, and keratinocytes and dermal blood endothelial cells were identified as its likely cellular sources. In an imiquimod-induced psoriasis-like mouse model, CCL7 had a profound impact on myeloid cell inflammation as well as on the upregulation of key pro-psoriatic cytokines such as CCL20, IL-12p40 and IL-17C, while its blockade led to an increase in the antipsoriatic cytokine IL-4. In humans receiving the TNF-α-blocker infliximab, CCL7 was downregulated in lesional psoriatic skin already within 16 hours after a single intravenous infusion. These data suggest that CCL7 acts as a driver of TNF-α-dependent Th1/Th17-mediated inflammation in lesional psoriatic skin.
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Brunner
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Glitzner
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Baerbel
authors.initials: B
authors.lastname: Reininger
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Klein
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Stary
authors.affiliation: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Pavel
authors.initials: P
authors.lastname: Uhrin
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D054410:Chemokine CCL7 / Q000235:genetics / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation; D042783:Endothelial Cells / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D000069285:Infliximab / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012871:Skin Diseases / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055815:Young Adult
chemical_list: C515450:CCL7 protein, human; C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: CCL7; TNF-α; chemokines; myeloid cells; psoriasis