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

Cited by 7 publications

(3 citation statements)

References 53 publications

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“…Our results are also in line with preclinical studies demonstrating a downregulation of proinflammatory cytokines production following treatment with vitamin D [30][31][32]. Corrado et al recently demonstrated that 25OHD supplementation was associated with a significant reduction of IL-17A and pro-fibrotic cytokines (FGF2, TGFβ, CTGF) both in patients with systemic sclerosis and in healthy subjects, with a dose-dependent effect [33]. On the other hand, clinical data showed inconsistent results on serum IL-17 and Th-17 cells in subjects with neurologic conditions [8][9][10].…”

Section: Discussionsupporting

confidence: 91%

Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency

et al. 2022

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The effects of different cholecalciferol supplementation regimens on serum inflammatory cytokines in healthy subjects with vitamin D deficiency are still lacking. This is a single-center, open-label, randomized, parallel group study involving healthy subjects deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. IL-17A, IL-6, IL-8, IL-10, IL-23 and TNFα were measured at baseline and at week 4, 8, 12, and 16. 75 healthy subjects were enrolled (58.7% female), with an average age of 34.1 ± 10.2 years. No statistical differences were observed among groups at baseline for either IL-6, IL-17A, IL-23, IL-8 or IL-10 at any time point; TNFα was indetectable. Concerning the whole sample, the time trend analysis showed a statistically significant linear trend for decreasing values over the treatment period for IL-6 (p = 0.016) and IL-17A (p = 0.006), while no significant time trends were observed for the other teste cytokines. No significant differences were found in the serum concentrations of the tested cytokines between week 12 and week 16. In young healthy individuals deficient in vitamin D, cholecalciferol administration showed a decrease in the serum IL-6 and IL-17A concentrations, without marked differences using the three regimens.

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Section: Discussionsupporting

confidence: 91%

Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency

et al. 2022

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“…Clinical studies have provided evidence that vit D has the ability to inhibit both IL-17A and pro-fibrotic cytokines, indicating its potential anti-fibrotic effect [25]. These findings support the hypothesis that vit D supplementation in SSc patients may have a potentially beneficial effect on fibrotic processes by inhibiting the production of these cytokines.…”

Section: Discussionsupporting

confidence: 64%

Vitamin D3 and Α-Tocopherol Acetate Ameliorate Inflammatory and Fibrotic Processes in Systemic Sclerosis: Preclinical Evidence

Doskaliuk

Zaiats

Gupta

2023

Proc Shevchenko Sci Soc Med Sci

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Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vascular abnormalities. Despite extensive research, there is currently no effective treatment for SSc. This study aimed to investigate the effects of α-tocopherol acetate and vitamin D3 on the levels of surfactant protein D (SP-D), interleukin-13 (IL-13), and vascular cell adhesion molecule-1 (VCAM-1) in a preclinical model of SSc. The study included an intact group (IG) (15 animals) with no interventions, control group (CG) (20 animals) injected with isotonic solution, an experimental group #1 (EG#1) (25 animals) that were induced with SSc by injecting them subcutaneously with 0.5 ml of 5% (NaClO) three times a week for six consecutive weeks; and experimental group #2 (EG#2) (25 animals) with correction provided by injections of vitamin D (1000 IU / 100 g) and α-tocopherol acetate (10 mg / 100 g ) intramuscularly for 3 weeks. The serum concentrations of IL-13, SP-D, and VCAM-1 were significantly higher in the EG#1 compared to the control group (109.35 (93,23-199.05) vs 8.50 (5.60-14.20), p=0.004; 490.20 (156.20-605.70) vs 78.10 (40.80-100.40), p=0.004; 91.25 (85.00 -264.98) vs 19.50 (13.53-22.20), p=0.004 respectively). The administration of vitamin D3 and α-tocopherol acetate was found to have a positive effect on all three parameters investigated. The SP-D level in the EG#2 was significantly lower than that in the EG#1 (490.20 (156.20-605.70) vs 123.75 (108.80-145.03), p=0.004). The concentration of IL-13 and VCAM-1 were also lower in the EG#2. In conclusion, this study provides evidence of the beneficial effects of vitamin D3 and α-tocopherol acetate in reducing the levels of SP-D, IL-13, and VCAM-1 in a preclinical model of systemic sclerosis.

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“…In animal SSc models, various cytokines, chemokines, lymphocytes, and monocytes show elevated expression levels. In cellular experiments related to SSc, the imbalance of different cells and cytokines directly affects fibrosis, either promoting or inhibiting it [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis

Wang,

Oishi,

Kobayashi

et al. 2024

IJMS

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The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription–polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.

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

Cited by 7 publications

References 53 publications

Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency

Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency

Vitamin D3 and Α-Tocopherol Acetate Ameliorate Inflammatory and Fibrotic Processes in Systemic Sclerosis: Preclinical Evidence

The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis

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