Vitamin D effects on monocytes’ CCL-2, IL6 and CD14 transcription in Addison’s disease and HLA susceptibility

Kraus, Anna; Penna-Martinez, Marissa; Meyer, Gesine; Badenhoop, Klaus

doi:10.1016/j.jsbmb.2017.07.026

Cited by 8 publications

(9 citation statements)

References 53 publications

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“…Since DQA1 is in linkage-disequilibrium with DQB1 the extended genotype was determined and categorized in three different risk groups depending on DQ2 and/or DQ8 presence or absence. According to our previous work ( 10 , 24 ) and congruent findings from others ( 9 , 11 ) high-risk HLA was defined as HLA homozygous DQ2/DQ2, homozygous DQ8/DQ8 and DQ2/DQ8, heterozygous HLA DQ2/x and HLA DQ8/x as intermediate‐risk HLA and any other haplotype (x/x) as low-risk HLA.…”

Section: Methodsmentioning

confidence: 66%

“…no 130-093-897; Miltenyi Biotech) as an inflammatory stimulant, and/or 1 × 10 −8 mol/L 1,25(OH) 2 D 3 (Enzo, Lörrach, Germany) for demonstrating the vitamin D-regulating effect in stimulated monocytes, or 1 × 10 −8 mol/L 1,25(OH) 2 D 3 was added alone without IL1β, in comparison to untreated cells, for demonstrating the vitamin D-regulating effect in resting monocytes. Dose and exposure time of 1,25(OH) 2 D 3 and IL1β was based upon our previous work ( 24 ).…”

Section: Methodsmentioning

confidence: 99%

“…The experimental part regarding IL-6 und CCL-2 mRNA expression, as well as CD14 expression in 13 AD/AIT patients, has been published ( 24 ) and is therefore not repeated here.…”

Section: Methodsmentioning

confidence: 99%

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Monocytic Cytokines in Autoimmune Polyglandular Syndrome Type 2 Are Modulated by Vitamin D and HLA-DQ

et al. 2020

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ContextAutoimmune polyglandular syndrome (APS-2: autoimmune Addison’s disease or type 1 diabetes) is conferred by predisposing HLA molecules, vitamin D deficiency, and heritable susceptibility. Organ destruction is accompanied by cytokine alterations. We addressed the monocytic cytokines of two distinct APS-2 cohorts, effects of vitamin D and HLA DQ risk.MethodsAPS-2 patients (n = 30) and healthy controls (n = 30) were genotyped for HLA DQA1/DQB1 and their CD14+ monocytes stimulated with IL1β and/or 1,25(OH)2D3 for 24 h. Immune regulatory molecules (IL-6, IL-10, IL-23A, IL-15, CCL-2, PD-L1), vitamin D pathway gene transcripts (CYP24A1, CYP27B1, VDR), and CD14 were analyzed by enzyme-linked immunosorbent assay and RTqPCR.ResultsPro-inflammatory CCL-2 was higher in APS-2 patients than in controls (p = 0.001), whereas IL-6 showed a trend – (p = 0.1). In vitro treatment with 1,25(OH)2D3 reduced proinflammatory cytokines (IL-6, CCL-2, IL-23A, IL-15) whereas anti-inflammatory cytokines (IL-10 and PD-L1) rose both in APS-type 1 diabetes and APS-Addison´s disease. Patients with adrenal autoimmunity showed a stronger response to vitamin D. Expression of IL-23A and vitamin D pathway genes VDR and CYP27B1 varied by HLA genotype and was lower in healthy individuals with high-risk HLA (p = 0.0025; p = 0.04), while healthy controls with low-risk HLA showed a stronger IL-10 and CD14 expression (p = 0.01; p = 0.03).Conclusion1,25(OH)2D3 regulates the monocytic response in APS-2 disorders type 1 diabetes or Addison´s disease. The monocytic cytokine profile of individuals carrying HLA high-risk alleles is proinflammatory, enhances polyglandular autoimmunity and can be targeted by vitamin D.

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Section: Methodsmentioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

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Monocytic Cytokines in Autoimmune Polyglandular Syndrome Type 2 Are Modulated by Vitamin D and HLA-DQ

et al. 2020

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“…AD clinically occurs with adrenal insufficiency, caused by an autoimmune-mediated destruction of adrenal cortex [217]. Although the pathogenesis of AD has not been completely elucidated, an interplay role between HLA haplotypes and environmental factors has been postulated [218,219]. In addition, different genes responsible for vitamin D metabolism and VDR gene polymorphisms are implicated in AD onset [220][221][222][223].…”

Section: Addison's Diseasementioning

confidence: 99%

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

et al. 2020

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Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

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“…Since DQA1 is in linkage-disequilibrium with DQB1 the extended genotype was determined and categorized in three different risk groups depending on DQ2 and/or DQ8 presence or absence. According to our previous work (10,24) and congruent findings from others (9, 11) high-risk HLA was defined as HLA homozygous DQ2/DQ2, homozygous DQ8/DQ8 and DQ2/DQ8, heterozygous HLA DQ2/x and HLA DQ8/x as intermediate-risk HLA and any other haplotype (x/x) as low-risk HLA.…”

Section: Hla Dq Genotypingmentioning

confidence: 80%

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Vitamin D effects on monocytes’ CCL-2, IL6 and CD14 transcription in Addison’s disease and HLA susceptibility

Cited by 8 publications

References 53 publications

Monocytic Cytokines in Autoimmune Polyglandular Syndrome Type 2 Are Modulated by Vitamin D and HLA-DQ

Monocytic Cytokines in Autoimmune Polyglandular Syndrome Type 2 Are Modulated by Vitamin D and HLA-DQ

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

Table_1.docx

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