Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts.
Cristina AntinozziPaolo SgròFrancesco MaramponDaniela CaporossiFrancesco Del GaldoIvan DimauroLuigi Di LuigiPublished in: Biology (2021)
Oxidative stress plays a key role in systemic sclerosis (SSc) pathogenesis, and an altered redox homeostasis might be responsible for abnormal inflammatory status, fibrosis and tissue damage extension. In this study, we explored the effect of the phosphodiesterase type 5 inhibitor sildenafil in modulating the activation of the CXCL-9, -10, -11/CXCR3 axis, which is fundamental in the perpetuation of inflammation in different autoimmune diseases, in the cell culture of SSc human dermal fibroblasts exposed to a pro-oxidant environment. We observed that sildenafil significantly reduced gene expression and release of CXCL-9, -10 and -11, inhibited the CXCR3 action and suppressed the activation of STAT1-, JNK- and p38MAPK pathways. This in vitro study on dermal fibroblasts supports clinical studies to consider the efficacy of sildenafil in preventing tissue damage and fibrosis in SSc by targeting central biomarkers of disease progression, vascular injuries and fibrosis and reducing the pro-inflammatory activation induced by oxidative stress.
Keyphrases
- oxidative stress
- systemic sclerosis
- pulmonary hypertension
- gene expression
- pulmonary arterial hypertension
- interstitial lung disease
- induced apoptosis
- reactive oxygen species
- dna damage
- ischemia reperfusion injury
- diabetic rats
- signaling pathway
- extracellular matrix
- dna methylation
- endothelial cells
- cell death
- rheumatoid arthritis
- anti inflammatory
- cell proliferation
- liver fibrosis
- induced pluripotent stem cells