Iloprost Attenuates Oxidative Stress-Dependent Activation of Collagen Synthesis Induced by Sera from Scleroderma Patients in Human Pulmonary Microvascular Endothelial Cells

Giordo, Roberta; Thuan, Duong Thi Bich; Posadino, Anna Maria; Cossu, Annalisa; Zinellu, Angelo; Erre, Gian Luca; Pintus, Gianfranco

doi:10.3390/molecules26164729

Cited by 10 publications

(8 citation statements)

References 65 publications

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“…SSc patients have a chronic hypoperfusion that improves after Iloprost infusion, both in the skin and in the internal organs [ 8 , 9 ]. Furthermore, Iloprost has been shown to have a long-lasting endothelium protective effect [ 11 ]. Prolonged hypoperfusion contributes to activation of inflammatory signals and oxidative stress, thereby accelerating injury and fibrosis in skin and kidney.…”

Section: Discussionmentioning

confidence: 99%

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Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Pellicano,

Colalillo,

De Marco

et al. 2024

Clin Exp Med

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Introduction Systemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost. Methods Twenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2). Results SSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC. Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2. Conclusions SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.

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Section: Discussionmentioning

confidence: 99%

“…Iloprost induces vasodilation, anti-platelet aggregation, cytoprotection, antioxidant effect and immunomodulation. These effects ameliorate the small vessel vasculopathy [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Pellicano,

Colalillo,

De Marco

et al. 2024

Clin Exp Med

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“…These oxidative molecules not only induced oxidative stress but enhanced collagen synthesis by human pulmonary smooth muscle cells [ 124 ]. Recently, Giordo et al [ 125 ] found that Iloprost (a stable analog of prostacyclin) could attenuate SSc serum-induced collagen synthesis by human pulmonary microvascular-endothelial cells via anti-oxidant mechanisms.…”

Section: The Molecular Basis Of Accelerated Inflamm-aging In Patients With Sscmentioning

confidence: 99%

Molecular Basis of Accelerated Aging with Immune Dysfunction-Mediated Inflammation (Inflamm-Aging) in Patients with Systemic Sclerosis

Shen

et al. 2021

Cells

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Systemic sclerosis (SSc) is a chronic connective tissue disorder characterized by immune dysregulation, chronic inflammation, vascular endothelial cell dysfunction, and progressive tissue fibrosis of the skin and internal organs. Moreover, increased cancer incidence and accelerated aging are also found. The increased cancer incidence is believed to be a result of chromosome instability. Accelerated cellular senescence has been confirmed by the shortening of telomere length due to increased DNA breakage, abnormal DNA repair response, and telomerase deficiency mediated by enhanced oxidative/nitrative stresses. The immune dysfunctions of SSc patients are manifested by excessive production of proinflammatory cytokines IL-1, IL-6, IL-17, IFN-α, and TNF-α, which can elicit potent tissue inflammation followed by tissue fibrosis. Furthermore, a number of autoantibodies including anti-topoisomerase 1 (anti-TOPO-1), anti-centromere (ACA or anti-CENP-B), anti-RNA polymerase enzyme (anti-RNAP III), anti-ribonuclear proteins (anti-U1, U2, and U11/U12 RNP), anti-nucleolar antigens (anti-Th/T0, anti-NOR90, anti-Ku, anti-RuvBL1/2, and anti-PM/Scl), and anti-telomere-associated proteins were also found. Based on these data, inflamm-aging caused by immune dysfunction-mediated inflammation exists in patients with SSc. Hence, increased cellular senescence is elicited by the interactions among excessive oxidative stress, pro-inflammatory cytokines, and autoantibodies. In the present review, we will discuss in detail the molecular basis of chromosome instability, increased oxidative stress, and functional adaptation by deranged immunome, which are related to inflamm-aging in patients with SSc.

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“…Of note, treatment with TAK1 inhibitor HS‐276 prevented dermal and pulmonary fibrosis and reduced the expression of profibrotic mediators in bleomycin‐treated mice 167 . Among antioxidants, NAC showed therapeutic benefit in a subset of patients with PSS 168,169 and ILD 170–172 . Iloprost, a stable analog of PGI2, is an established therapy for skin and pulmonary manifestations in patients with PSS.…”

Section: Introductionmentioning

confidence: 99%

Redox Pathogenesis in Rheumatic Diseases

Laniak,

Winans,

Patel

et al. 2024

ACR Open Rheumatology

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Despite being some of the most anecdotally well‐known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end‐organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions.

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Iloprost Attenuates Oxidative Stress-Dependent Activation of Collagen Synthesis Induced by Sera from Scleroderma Patients in Human Pulmonary Microvascular Endothelial Cells

Cited by 10 publications

References 65 publications

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Molecular Basis of Accelerated Aging with Immune Dysfunction-Mediated Inflammation (Inflamm-Aging) in Patients with Systemic Sclerosis

Redox Pathogenesis in Rheumatic Diseases

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