{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:24:00Z","timestamp":1789503840885,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University of Rome","award":["000031_19_rs_"],"award-info":[{"award-number":["000031_19_rs_"]}]},{"name":"Sapienza University of Rome","award":["RBSI14D5NX"],"award-info":[{"award-number":["RBSI14D5NX"]}]},{"name":"Scientific Independence of young Researchers (SIR)","award":["000031_19_rs_"],"award-info":[{"award-number":["000031_19_rs_"]}]},{"name":"Scientific Independence of young Researchers (SIR)","award":["RBSI14D5NX"],"award-info":[{"award-number":["RBSI14D5NX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The prostacyclin analogue iloprost is used to treat vascular alterations and digital ulcers, the early derangements manifesting in systemic sclerosis (SSc), an autoimmune disease leading to skin and organ fibrosis. Bioindicator(s) of SSc onset and progress are still lacking and the therapeutic approach remains a challenge. The T helper 1 (Th1) chemokine interferon (IFN)\u03b3-induced protein 10 (IP-10\/CXCL10) associates with disease progression and worse prognosis. Endothelial cells and fibroblasts, under Th1-dominance, release CXCL10, further enhancing SSc\u2019s detrimental status. We analyzed the effect of iloprost on CXCL10 in endothelial cells, dermal fibroblasts, and in the serum of SSc patients. Human endothelial cells and dermal fibroblasts activated with IFN\u03b3\/Tumor Necrosis Factor (TNF)\u03b1, with\/without iloprost, were investigated for CXCL10 secretion\/expression and for intracellular signaling cascade underlying chemokine release (Signal Transducer and Activator of Transcription 1, STAT1; Nuclear Factor kappa-light-chain-enhancer of activated B cells, NF-kB; c-Jun NH2-terminal kinase, JNK: Phosphatidyl-Inositol 3-kinase (PI3K)\/protein kinase B, AKT; Extracellular signal-Regulated Kinase 1\/2, ERK1\/2). CXCL10 was quantified in sera from 25 patients taking iloprost, satisfying the American College of Rheumatology (ACR)\/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria for SSc, and in sera from 20 SSc sex\/age-matched subjects without therapy, previously collected. In human endothelial cells and fibroblasts, iloprost targeted CXCL10, almost preventing IFN\u03b3\/TNF\u03b1-dependent cascade activation in endothelial cells. In SSc subjects taking iloprost, serum CXCL10 was lower. These in vitro and in vivo data suggest a potential role of iloprost to limit CXCL10 at local vascular\/dermal and systemic levels in SSc and warrant further translational research aimed to ameliorate SSc understanding\/management.<\/jats:p>","DOI":"10.3390\/ijms231710150","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Prostacyclin Analogue Iloprost Modulates CXCL10 in Systemic Sclerosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4413-1817","authenticated-orcid":false,"given":"Tania","family":"Colasanti","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4209-8942","authenticated-orcid":false,"given":"Katia","family":"Stefanantoni","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Fantini","sequence":"additional","affiliation":[{"name":"Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome \u201cForo Italico\u201d, Piazza Lauro de Bosis, 006-00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Corinaldesi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome \u201cForo Italico\u201d, Piazza Lauro de Bosis, 006-00135 Rome, Italy"},{"name":"Institute for Cancer Genetics, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Vasile","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marampon","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Sapienza University of Rome, Viale del Policlinico, 155-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2522-126X","authenticated-orcid":false,"given":"Luigi","family":"Di Luigi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome \u201cForo Italico\u201d, Piazza Lauro de Bosis, 006-00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-5081","authenticated-orcid":false,"given":"Cristina","family":"Antinozzi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome \u201cForo Italico\u201d, Piazza Lauro de Bosis, 006-00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4929-2764","authenticated-orcid":false,"given":"Paolo","family":"Sgr\u00f2","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome \u201cForo Italico\u201d, Piazza Lauro de Bosis, 006-00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lenzi","sequence":"additional","affiliation":[{"name":"Department of 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