1,25OH-Vitamin D3 and IL-17 Inhibition Modulate Pro-Fibrotic Cytokines Production in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis

Corrado, Addolorata; Rotondo, Cinzia; Sanpaolo, Eliana Rita; Altomare, Alberto; Maruotti, Nicola; Cici, Daniela; Cantatore, Francesco Paolo

doi:10.7150/ijms.70984

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Int J Med Sci 2022; 19(5):867-877. doi:10.7150/ijms.70984 This issue Cite

Research Paper

1,25OH-Vitamin D3 and IL-17 Inhibition Modulate Pro-Fibrotic Cytokines Production in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis

Addolorata Corrado^*✉, Cinzia Rotondo^*, Eliana Rita Sanpaolo, Alberto Altomare, Nicola Maruotti, Daniela Cici, Francesco Paolo Cantatore

Rheumatology Clinic - Department of Medical and Surgical Sciences, University of Foggia, Foggia- Italy
*These authors contributed equally to this work.

Citation:

Corrado A, Rotondo C, Sanpaolo ER, Altomare A, Maruotti N, Cici D, Cantatore FP. 1,25OH-Vitamin D3 and IL-17 Inhibition Modulate Pro-Fibrotic Cytokines Production in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis. Int J Med Sci 2022; 19(5):867-877. doi:10.7150/ijms.70984. https://www.medsci.org/v19p0867.htm

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Abstract

Objectives: IL-17 modulates the synthesis of several molecules involved in the pathogenesis of Systemic Sclerosis (SSc). Vitamin D (1,25(OH)₂D3) shows anti-fibrotic properties and it is able to affect the IL-17 production in several experimental conditions.

The aim of this study is to assess the production of IL-17A and pro-fibrotic cytokines in peripheral blood mononuclear cells (PBMCs) from subjects with SSc in basal conditions and after treatment with 1,25(OH)2D3 and IL-17A neutralizing antibodies.

Methods: The production of IL-17A and pro-fibrotic cytokines (TGFβ, CTGF and FGF2) in PBMCs obtained from 51 SSc patients and 31 healthy subjects was assessed both in basal conditions and in presence of anti-IL17A antibodies and several concentrations of 1,25(OH)₂D3. The association of cytokines production with clinical disease characteristics and the in vitro effect of 1,25(OH)₂D3 and IL-17A inhibition were assessed.

Results: PBMCs from SSc subjects produced higher amount IL-17A, TGFβ, CTGF and FGF2 compared to healthy controls. IL17, TGFβ, CTGF and FGF2 levels were higher in SSc patients with interstitial lung disease and digital ulcers, whereas IL-17A production was lower in patients with PAH. IL- 17A inhibition reduced the production of FGF2, whereas enhanced the synthesis of TGFβ and CTGF. 1,25(OH)₂D3 decreased the production of IL17A and pro-fibrotic cytokines in a dose- dependent manner.

Conclusions: IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)₂D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.

Keywords: Systemic Sclerosis, T-lymphocytes, Interleukins, Fibrosis

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APA

Corrado, A., Rotondo, C., Sanpaolo, E.R., Altomare, A., Maruotti, N., Cici, D., Cantatore, F.P. (2022). 1,25OH-Vitamin D3 and IL-17 Inhibition Modulate Pro-Fibrotic Cytokines Production in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis. International Journal of Medical Sciences, 19(5), 867-877. https://doi.org/10.7150/ijms.70984.

ACS

Corrado, A.; Rotondo, C.; Sanpaolo, E.R.; Altomare, A.; Maruotti, N.; Cici, D.; Cantatore, F.P. 1,25OH-Vitamin D3 and IL-17 Inhibition Modulate Pro-Fibrotic Cytokines Production in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis. Int. J. Med. Sci. 2022, 19 (5), 867-877. DOI: 10.7150/ijms.70984.

NLM

CSE

Corrado A, Rotondo C, Sanpaolo ER, Altomare A, Maruotti N, Cici D, Cantatore FP. 2022. 1,25OH-Vitamin D3 and IL-17 Inhibition Modulate Pro-Fibrotic Cytokines Production in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis. Int J Med Sci. 19(5):867-877.

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