title: Proinflammatory effects of diesel exhaust nanoparticles on scleroderma skin cells.
abstract: Autoimmune diseases are complex disorders of unknown etiology thought to result from interactions between genetic and environmental factors. We aimed to verify whether environmental pollution from diesel engine exhaust nanoparticulate (DEP) of actually operating vehicles could play a role in the development of a rare immune-mediated disease, systemic sclerosis (SSc), in which the pathogenetic role of environment has been highlighted. The effects of carbon-based nanoparticulate collected at the exhaust of newer (Euro 5) and older (Euro 4) diesel engines on SSc skin keratinocytes and fibroblasts were evaluated in vitro by assessing the mRNA expression of inflammatory cytokines (IL-1 α , IL-6, IL-8, and TNF-α) and fibroblast chemical mediators (metalloproteases 2, 3, 7, 9, and 12; collagen types I and III; VEGF). DEP was shown to stimulate cytokine gene expression at a higher extent in SSc keratinocytes versus normal cells. Moreover, the mRNA gene expression of all MMPs, collagen types, and VEGF genes was significantly higher in untreated SSc fibroblasts versus controls. Euro 5 particle exposure increased the mRNA expression of MMP-2, -7, and -9 in SSc fibroblasts in a dose dependent manner and only at the highest concentration in normal cells. We suggest that environmental DEP could trigger the development of SSc acting on genetically hyperreactive cell systems.
authors: Laboratorio di Fisiopatologia Cutanea, Istituto Dermatologico S Gallicano, Via E. Chianesi 53, 00144 Roma, Italy.
authors: A
authors: A
authors: Mastrofrancesco
authors: Istituto di Ricerche sulla Combustione (IRC), CNR, Piazzale V. Tecchio 80, 80125 Napoli, Italy.
authors: M
authors: M
authors: Alfè
authors: Dipartimento di Medicina Clinica, Università Sapienza, CNR, Viale dell'Università 37, 00185 Roma, Italy.
authors: E
authors: E
authors: Rosato
authors: Istituto di Ricerche sulla Combustione (IRC), CNR, Piazzale V. Tecchio 80, 80125 Napoli, Italy.
authors: V
authors: V
authors: Gargiulo
authors: Istituto Motori (IM), Via Marconi 8, 80125 Napoli, Italy.
authors: C
authors: C
authors: Beatrice
authors: Istituto Motori (IM), Via Marconi 8, 80125 Napoli, Italy.
authors: G
authors: G
authors: Di Blasio
authors: Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China.
authors: B
authors: B
authors: Zhang
authors: Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China.
authors: D S
authors: DS
authors: Su
authors: Laboratorio di Fisiopatologia Cutanea, Istituto Dermatologico S Gallicano, Via E. Chianesi 53, 00144 Roma, Italy.
authors: M
authors: M
authors: Picardo
authors: Dipartimento di Medicina Clinica, Università Sapienza, CNR, Viale dell'Università 37, 00185 Roma, Italy.
authors: S
authors: S
authors: Fiorito
mesh_terms: D016022:Case-Control Studies; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D059647:Gene-Environment Interaction; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000032:analysis / Q000633:toxicity*; D052638:Particulate Matter / Q000302:isolation & purification / Q000494:pharmacology*; D061251:Primary Cell Culture; D012595:Scleroderma, Systemic / Q000235:genetics / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053260:Soot / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D001335:Vehicle Emissions / Q000032:analysis
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C508600:IL6 protein, human; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016209:Interleukin-8; D052638:Particulate Matter; D053260:Soot; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D001335:Vehicle Emissions; D017364:Collagenases