title: Keratinocytes from patients with atopic dermatitis and psoriasis show a distinct chemokine production profile in response to T cell-derived cytokines.
abstract: BACKGROUND
  Atopic dermatitis (AD) and psoriasis are genetically determined inflammatory skin disorders. Keratinocytes actively participate in cutaneous inflammatory responses by elaborating various chemokines.
  
  
  OBJECTIVE
  We investigated the capacity of IL-4, IFN-gamma, and TNF-alpha to modulate the expression of CCL and CXCL chemokines in cultured keratinocytes from patients and healthy individuals, as well as chemokine expression in situ.
  
  
  METHODS
  Keratinocyte cultures were established from normal-looking skin of adult patients with AD or psoriasis vulgaris and from healthy subjects. Monocyte chemoattractant protein 1 (MCP-1)/CCL2, RANTES/CCL5, IL-8/CXCL8, and IFN-gamma-induced protein of 10 kd (IP-10)/CXCL10 production was evaluated at the mRNA and protein levels by using RNase protection assay and ELISA, respectively. The expression of the same chemokines was studied in chronic lesional skin by means of immunohistochemistry or in situ hybridization.
  
  
  RESULTS
  Only IL-8 mRNA was detected in unstimulated ke-ratinocyte cultures. MCP-1 and IP-10 were potently induced by IFN-gamma, whereas IL-8 and RANTES were preferentially upregulated by TNF-alpha and, to a lesser extent, by IFN-gamma. IL-4 weakly induced IP-10, RANTES, and IL-8 but not MCP-1. Keratinocytes of patients with AD invariably responded with significantly earlier and higher RANTES expression. By contrast, keratinocytes of patients with psoriasis displayed much higher levels of both constitutive and induced IL-8 and a stronger induction of MCP-1 and IP-10. RANTES and MCP-1 mRNA(+) keratinocytes were detected in the basal layer of lesions of patients with AD and psoriasis. IP-10 and IL-8 were consistently upregulated in the epidermis of patients with psoriasis but not in lesions of patients with AD.
  
  
  CONCLUSIONS
  Keratinocytes of patients with AD and psoriasis show an intrinsically abnormal and different chemokine production profile and may thus favor the recruitment of distinct leukocyte subsets into the skin.
authors.affiliation: Istituto Dermopatico dell'Immacolata, IRCCS, Roma, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Giustizieri
authors.forename: F
authors.initials: F
authors.lastname: Mascia
authors.forename: A
authors.initials: A
authors.lastname: Frezzolini
authors.forename: O
authors.initials: O
authors.lastname: De Pità
authors.forename: L M
authors.initials: LM
authors.lastname: Chinni
authors.forename: A
authors.initials: A
authors.lastname: Giannetti
authors.forename: G
authors.initials: G
authors.lastname: Girolomoni
authors.forename: S
authors.initials: S
authors.lastname: Pastore
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D018932:Chemokine CCL2; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000494:pharmacology*; D003876:Dermatitis, Atopic / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000145:classification; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001324:Autoantigens; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate