Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/ijms242015294
Keywords
human parvovirus B19 (B19); systemic sclerosis (SSc); VP1 unique region (VP1u); macrophages; fibrosis
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This study investigates the impacts of B19V-VP1u in macrophages and BLE-induced SSc mice. The results show that B19V-VP1u treatment decreases viability and migration of macrophages, while celastrol exerts an inhibitory effect. Additionally, B19V-VP1u exacerbates skin fibrosis in SSc mice, leading to increased expressions of inflammatory markers.
Human parvovirus B19 (B19V) is a single-stranded non-enveloped DNA virus of the family Parvoviridae that has been associated with various autoimmune disorders. Systemic sclerosis (SSc) is an autoimmune connective tissue disorder with high mortality and has been linked to B19V infection. However, the precise mechanism underlying the B19V contribution to the development of SSc remains uncertain. This study investigated the impacts of the functional B19V-VP1 unique region (VP1u) in macrophages and bleomycin (BLE)-induced SSc mice. Cell experimental data showed that significantly decreased viability and migration of both B19V-VP1u-treated U937 and THP-1 macrophages are detected in the presence of celastrol. Significantly increased MMP9 activity and elevated NF-kB, MMP9, IL-6, TNF-alpha, and IL-1 beta expressions were detected in both B19V-VP1u-treated U937 and THP-1 macrophages. Conversely, celastrol revealed an inhibitory effect on these molecules. Notably, celastrol intervened in this pathogenic process by suppressing the sPLA2 activity of B19V-VP1u and subsequently reducing the inflammatory response. Notably, the administration of B19V-VP1u exacerbated BLE-induced skin fibrosis in mice, with augmented expressions of TGF-beta, IL-6, IL-17A, IL-18, and TNF-alpha, ultimately leading to alpha-SMA and collagen I deposits in the dermal regions of BLE-induced SSc mice. Altogether, this study sheds light on parvovirus B19 VP1u linked to scleroderma and aggravated dermal fibrosis.
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