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.
Subject(s)
Fibroblasts/drug effects , Gene Expression/drug effects , Keratinocytes/drug effects , Nanoparticles/toxicity , Particulate Matter/pharmacology , Soot/pharmacology , Case-Control Studies , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type III/genetics , Collagen Type III/metabolism , Collagenases/genetics , Collagenases/metabolism , Dose-Response Relationship, Drug , Fibroblasts/metabolism , Gene-Environment Interaction , Humans , Inflammation/genetics , Inflammation/pathology , Interleukin-1alpha/genetics , Interleukin-1alpha/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Keratinocytes/metabolism , Nanoparticles/analysis , Particulate Matter/isolation & purification , Primary Cell Culture , Scleroderma, Systemic/genetics , Scleroderma, Systemic/pathology , Skin/drug effects , Skin/metabolism , Skin/pathology , Soot/isolation & purification , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vehicle Emissions/analysisABSTRACT
Five thousand eight hundred and thirty-seven healthy young men, aged 18-19, from two distinct regions of Central Italy, Abruzzo and Marche, have been investigated during the military medical examination to evaluate pigmentary traits and skin phototypes. They were examined over the entire body except the scalp and ano-genital area for pigmented lesions, which included common acquired melanocytic nevi (MN), clinically atypical nevi and solar lentigines. Eye and hair color were also recorded. Information was gathered by self-questionnaire, personal interview and clinical skin examination performed by two independent dermatologists. For sunlight susceptibility and sun exposure, each subject was classified from I to IV skin phototype according to the classification of sun-reactive skin types as proposed by Fitzpatrick. Almost half of the entire population (44.5%) had affirmed that they tanned easily and rarely burned (phototype IV), 10.3% had skin phototype I or II, 11.2% had more than 40 common MN, and 37.2% had atypical nevi with a diameter > or = 5 mm. The common MN and atypical nevi count had a significant association with skin phototype. Subjects with phototype I or II, and solar lentigo had significantly higher nevus counts than individuals without these characteristics.
