Metabolism of 25-Hydroxy-Vitamin D in Human Macrophages Is Highly Dependent on Macrophage Polarization

Nygaard, Rie; Nielsen, Marlene Christina; Antonsen, Kristian W.; Højskov, Carsten S.; Sørensen, Boe Sandahl; Møller, Holger Jon

doi:10.3390/ijms231810943

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…The presented results provide evidence that both catabolic pathways, via 24-hydroxylase enzyme into 24,25(OH) 2 D and 1,24,25(OH) 3 D, considered as inert metabolites, and via C3-epimerase catabolic pathway [ 22 , 23 ] resulting in 3-epi-25(OH)D 3 synthesis, are engaged in the catabolism of VD in BC patients, similar to healthy subjects.…”

Section: Discussionmentioning

confidence: 66%

“…Vitamin D is catabolized mainly by the transformation of 1,25(OH) 2 D and its precursor 25(OH)D via 24-hydroxylase enzyme into 24,25(OH) 2 D and 1,24,25(OH) 3 D derivatives, known as inactive metabolites. Far less information is available about the function of the C 3 -epimerase catabolic pathway [ 22 , 23 ], resulting in 3-epi-25(OH)D 3 synthesis. However, due to different impacts on calcium and bone metabolism [ 24 ], distinguishing between 25(OH)D 3 and the C-3 epimer is considered of biological importance [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D and Its Metabolites Status before and during Chemotherapy in Caucasian Breast Cancer Patients

Kimsa-Furdzik,

Bednarek,

Hibner

et al. 2023

Metabolites

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Background: The predictive role of vitamin D (VD) in breast cancer (BC) patients’ survival is still being investigated. This paper aims to evaluate the changes in VD metabolites during chemotherapy (CTH) and the predictive role of VD status in Caucasian BC patients treated with CTH. Methods: Vitamin D and its metabolites were assessed with reference LC–MS/MS methodology in 98 consecutive BC patients starting CHT, after 3 and 6 months, and compared to the control group. Results: The frequency of VD deficiency in BC patients was greater than in the control group (56.1% vs. 37.2%). After 6 months of CTH, the number of VD-deficient BC patients slightly increased to 60%. The concentrations of VD active forms [25(OH)D2, 25(OH)D3], and catabolites [24,25(OH)2D3 and 3-epi-25(OH)D3] decreased after 3 and 6 months of CTH compared to the baseline values. Strong positive correlations between concentrations of 3-epi-25(OH)D3 and 25(OH)D in both groups were found. Similar correlations were also observed between 24,25(OH)2D3 and 25(OH)D levels. Kaplan–Meier survival analysis showed significantly longer survival in BC patients without deficiency (>20 ng/mL) at baseline (HR = 2.44 (95% CI 1.07–5.59), p = 0.026). Conclusions: (1) Our data provide further evidence that BC patients before CTH are more VD-deficient than the general population and this deficiency increases further during CTH treatment, as observed using the reference LC-MS methodology. (2) Presented results show that VD catabolism is not affected in BC patients. (3) The poorer survival in VD-deficient BP patients supports the importance of VD supplementation in BC patients with 25(OH)D levels below 20 ng/mL.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Vitamin D and Its Metabolites Status before and during Chemotherapy in Caucasian Breast Cancer Patients

Kimsa-Furdzik,

Bednarek,

Hibner

et al. 2023

Metabolites

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“…6C, we examined the gene expression of several anti-inflammatory cytokines (Il4, Il10) and pro-inflammatory cytokines (Tnfa, Il17b, Il6, and Il1b) in the spleen, which was the tissue with the highest 1,25(OH) 2 D 3 concentration demonstrated by both MSI and confirmatory tissue homogenate. 1,25(OH) 2 D 3 has been shown to suppress the proinflammatory cytokines like Tnfa and Il17b and increase anti-inflammatory cytokines like Il4 and Il10 in macrophages and T cells during polarization, inflammatory disease, and cell differentiation (31)(32)(33)(34). We found that Il4 was significantly increased in the spleen, whereas Tnfa was suppressed.…”

Section: Gene Expression Consequences Of Elevated Tissue 125(oh) 2 Dmentioning

confidence: 60%

Spatial detection and consequences of nonrenal calcitriol production as assessed by targeted mass spectrometry imaging

Meyer,

Lee,

Cichanski

et al. 2024

JCI Insight

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The immune benefits of vitamin D 3 supplementation beyond calcium and phosphate maintenance are highly clinically debated. Kidney expression of CYP27B1 is the source of endocrine, circulating 1,25(OH) 2 D 3 (active form of vitamin D) that maintains serum calcium and phosphate. 1,25(OH) 2 D 3 may also be made by the CYP27B1 enzyme in nonrenal cells, like immune cells, in a process driven by cellular availability of 25(OH)D 3 and inflammation. Due to the endocrine nature of 1,25(OH) 2 D 3 in circulation, it is difficult to discern between these 2 sources. We recently created a regulatory deletion model of Cyp27b1 (M1/M21-DIKO) where mice have normal inflammatory-regulated Cyp27b1 expression in nonrenal tissues (unlike global Cyp27b1 -KO) but no expression within the kidney. Here, utilizing on-tissue chemical derivatization and matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), we investigated the distribution of 1,25(OH) 2 D 3 and 25(OH)D 3 in the kidney, liver, spleen, and thymus. MALDI-MSI demonstrated increased 1,25(OH) 2 D 3 in nonrenal tissues such as the spleen after vitamin D 3 supplementation in M1/M21-DIKO mice. Additionally, from this, we found increased Il4 and decreased Tnfa in the spleen after vitamin D 3 supplementation. Taken together, these data demonstrate nonrenal production of 1,25(OH) 2 D 3 in vivo and provide a consequence of vitamin D 3 supplementation and nonrenal 1,25(OH) 2 D 3 production in cytokine changes.

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“…Применительно к дендритным клеткам и тканевым макрофагам эффекты лиганд-ассоциированной активации VDR в наибольшей степени изучены, среди всех иммунокомпетентных клеток, однако, опять же большинство представленных в литературе данных не основывается непосредственно на изменениях, касающихся пародонта. Одной из предпосылок к подобному детальному изучения данных популяций клеток стало выявление в них экспрессии рецептора витамина D, а также доказательство способности этих клеток локально синтезировать активную форму витамина D за счет гидроксилаз CYP27B1 и CYP24A1 [ 53,54 ] . И то, и другое свидетельствует в пользу глубокой сопряженности лиганд-ассоциированных эффектов VDR с функциональной ролью дендритных клеток и макрофагов в качестве антигенпредставляющих клеток и клетокинициаторов адаптивного иммунного ответа.…”

Section: дендритные клетки и тканевые макрофагиunclassified

Current views on pathogenetic factors of periodontitis development and potential effects of ligand-associated activation of vitamin D receptors: literature review

Куликов,

Жадько,

Кривенцов

2023

Clinical Dentistry (Russia)

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Пародонтит как сложное и многофакторное заболевание с нелинейным характером прогрессирования и диспропорциональным иммунным ответом остается актуальной проблемой в стоматологии, в том числе в направлении поиска новых высокоэффективных методов коррекции и профилактики, включая патогенетически обоснованные подходы модуляции иммунного ответа организма. В обзоре литературы представлены современные ключевые патогенетические звенья и наиболее значимые, вовлеченные в реализацию поражения пародонта клеточные субпопуляции, с соответствующими потенциальными точками приложения лиганд-ассоциированной активации рецепторов витамина D. Имеющиеся в литературе данные указывают на выраженный противовоспалительный вектор эффектов витамина D и его аналогов, характеризующийся подавлением разрушения E-кадгериновых контактов кератиноцитов, индукцией поляризации клеток моноцитарно-макрофагального ряда в сторону противовоспалительного M2-фенотипа, стимуляцией сдвига в балансе Th1/Th2-клеток в сторону T-хелперов 2-го типа, а в балансе Th17/Treg — в сторону регуляторных T-лимфоцитов. Представленные данные ряда клинических исследований и метаанализов указывают на наличие статистически достоверно более низких уровней 25-гидроксивитамина D в крови у пациентов с хроническим пародонтитом по сравнению со здоровыми пациентами контрольных групп, хотя данные исследования характеризуются значительной гетерогенностью и вариабельностью. Имеющиеся в литературе данные указывают на наличие нескольких ключевых потенциальных точек приложения эффектов лиганд-ассоциированной активации рецепторов витамина D при пародонтите, объединенных общим противовоспалительным вектором иммуномодуляции и затрагивающих систему как неспецифического, так и адаптивного иммунного ответа. Существующие предпосылки диктуют необходимость проведения дополнительных экспериментальных и клинических исследований, направленных на выявление закономерностей изменения иммунной реактивности непосредственно в пародонте в условиях применения витамина D. Periodontitis, as a complex and multifactorial disease with a non-linear nature of progression and an imbalanced immune response, continues to be an urgent problem in dentistry, as well as the searching strategy for new highly effective methods of correction and prevention, including pathogenetically reasonable approaches to modulate the body’s immune response. The literature review presents modern key pathogenetic links and the most significant cellular subpopulations involved with the corresponding potential targets of vitamin D application. The available literature data indicate a pronounced anti-inflammatory vector of effects of vitamin D and its analogs, characterized by suppression of the destruction of E-cadherin contacts of keratinocytes, induction of polarization of monocytic and macrophageal cells towards the anti-inflammatory M2 phenotype, stimulation of a shift in the balance of Th1/Th2 cells towards T-helpers of the 2nd type, and in the balance of Th17/Treg towards regulatory T-lymphocytes. The presented data from a number of clinical studies and meta-analyses demonstrate the presence of statistically significantly lower blood levels of 25-hydroxyvitamin D in patients with chronic periodontitis compared with healthy controls, although these studies are characterized by significant heterogeneity and variability. . The available literature data indicate the presence of several key potential points of application of the effects of ligand-associated activation of vitamin D receptors in periodontitis, united by a common anti-inflammatory immunomodulation and affecting both nonspecific and adaptive immune responses. The existing prerequisites dictate the need for additional, both experimental and clinical studies aimed at identifying patterns of changes in immune reactivity directly in the periodontium under the conditions of vitamin D application.

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Metabolism of 25-Hydroxy-Vitamin D in Human Macrophages Is Highly Dependent on Macrophage Polarization

Cited by 6 publications

References 23 publications

Vitamin D and Its Metabolites Status before and during Chemotherapy in Caucasian Breast Cancer Patients

Vitamin D and Its Metabolites Status before and during Chemotherapy in Caucasian Breast Cancer Patients

Spatial detection and consequences of nonrenal calcitriol production as assessed by targeted mass spectrometry imaging

Current views on pathogenetic factors of periodontitis development and potential effects of ligand-associated activation of vitamin D receptors: literature review

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