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Parvovirus B19 activates in vitro normal human dermal fibroblasts: a possible implication in skin fibrosis and systemic sclerosis
- Source :
- Rheumatology (Oxford, England)
- Publication Year :
- 2020
- Publisher :
- Oxford University Press, 2020.
-
Abstract
- Objective Fibrosis is the most characteristic pathological hallmark of SSc, a connective tissue disease characterized by vascular and immunological abnormalities, inflammation and enhanced extracellular matrix production, leading to progressive fibrosis of skin and internal organs. We previously demonstrated that parvovirus B19 (B19V) can infect normal human dermal fibroblasts (NHDFs) and that B19V persists in SSc fibroblasts. In this study, we investigated whether parvovirus B19V is able to activate in vitro NHDFs and to induce in these cells some phenotypic features similar to that observed in the SSc fibroblasts. Methods We preliminarily analysed the time course of B19V infection in cultured NHDFs, then we investigated the ability of B19V to induce cell migration, invasive phenotype and mRNA expression of some profibrotic and/or proinflammatory genes. Results We confirmed our previous findings that B19V infects NHDFs, but the infection is not productive. After incubation with B19V, NHDFs showed a significant increase of both migration and invasiveness, along with mRNA expression of different profibrotic genes (α-SMA, EDN-1, IL-6, TGF-β1 receptors 1 and 2, Col1α2), some genes associated with inflammasome platform (AIM2, IFI16, IL-1β, CASP-1) and genes for metalloprotease (MMP 2, 9 and 12). Conclusion These data suggest that B19V can activate dermal fibroblasts and may have a role in the pathogenesis of fibrosis. B19V-induced fibroblast migration and invasiveness could be due to the B19V-associated MMP9 overexpression and activation. Moreover, the up-regulation of MMP12, typical of SSc, could link the B19V infection of fibroblasts to the anti-angiogenic process.
- Subjects :
- 0301 basic medicine
systemic sclerosis
Interleukin-1beta
parvovirus B19 infection
Pathogenesis
Extracellular matrix
0302 clinical medicine
Fibrosis
Cell Movement
Parvovirus B19, Human
Pharmacology (medical)
skin and connective tissue diseases
AcademicSubjects/MED00360
Cells, Cultured
Skin
integumentary system
Endothelin-1
Caspase 1
Nuclear Proteins
Inflammasome
Cell migration
normal human dermal fibroblasts
DNA-Binding Proteins
Matrix Metalloproteinase 9
030220 oncology & carcinogenesis
Matrix Metalloproteinase 2
fibrosi
medicine.drug
fibrosis
In Vitro Techniques
Collagen Type I
Fibroblast migration
Proinflammatory cytokine
Parvoviridae Infections
03 medical and health sciences
AIM2
Rheumatology
Matrix Metalloproteinase 12
medicine
Humans
RNA, Messenger
normal human dermal fibroblast
Inflammation
Basic and Translational Science
Scleroderma, Systemic
business.industry
Interleukin-6
Fibroblasts
medicine.disease
Phosphoproteins
Actins
030104 developmental biology
Cancer research
business
Transcriptome
Receptors, Transforming Growth Factor beta
Subjects
Details
- Language :
- English
- ISSN :
- 14620332 and 14620324
- Volume :
- 59
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Rheumatology (Oxford, England)
- Accession number :
- edsair.doi.dedup.....57d015927a7ba03712ba24ab76005aef