title: Inflammatory cells, cytokines and matrix metalloproteinases in amicrobial pustulosis of the folds and other neutrophilic dermatoses.
abstract: Amicrobial pustulosis of the folds (APF) is a rare cutaneous disease characterized by relapsing sterile pustules frequently associated with autoimmune disorders. Although APF pathophysiology is still undefined, scattered reports suggest involvement of neutrophils. The aim of the present study is to evaluate the role of the skin inflammatory infiltrate, selected multifunctional cytokines and effectors of tissue damage in APF and other neutrophilic dermatoses. We studied, by immunohistochemical methods, inflammatory cell markers (CD3, CD163, myeloperoxidase), cytokines (TNF-alpha, IL-8, IL-17), metalloproteinases (MMP-2, MMP-9) and vascular-endothelial-growth-factor (VEGF) in lesional skin from six patients with APF, 11 with pyoderma gangrenosum (PG), 7 with Sweet's syndrome, and in 20 normal skin samples. Immunoreactivities of CD3, CD163, myeloperoxidase, TNF-alpha, IL-8, IL-17, MMP-2, MMP-9 and VEGF were significantly higher in APF, PG and Sweet's syndrome than in controls (p=0.0001). IL-8 was more expressed in PG than in APF (P=0.002) and Sweet's syndrome (p=0.001). In APF, MMP-9 reactivity was higher than in Sweet's syndrome (p=0.035), but less intense than in PG (p=0.020). Our study supports the role of proinflammatory cytokines/chemokines and MMPs as important effectors for the tissue damage in APF similarly to classic neutrophilic dermatoses.
authors.affiliation: Unità Operativa di Dermatologia, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Università degli Studi di Milano, Italy.
authors.forename: A V
authors.initials: AV
authors.lastname: Marzano
authors.forename: M
authors.initials: M
authors.lastname: Cugno
authors.forename: V
authors.initials: V
authors.lastname: Trevisan
authors.forename: R
authors.initials: R
authors.lastname: Lazzari
authors.forename: D
authors.initials: D
authors.lastname: Fanoni
authors.forename: E
authors.initials: E
authors.lastname: Berti
authors.forename: C
authors.initials: C
authors.lastname: Crosti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000032:analysis*; D020381:Interleukin-17 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D009195:Peroxidase / Q000032:analysis; D010641:Phenotype; D011565:Psoriasis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D017511:Pyoderma Gangrenosum / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000032:analysis; D012867:Skin / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D016463:Sweet Syndrome / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D017252:CD3 Complex; C508606:CXCL8 protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D016209:Interleukin-8; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009195:Peroxidase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9