Loading...
 
Toggle Health Problems and D

Vitamin D Binding Protein may affect immune system dendritic cells – March 2022

Transcriptomic analysis reveal the responses of dendritic cells to VDBP

Genes Genomics. 2022 Mar 12. doi: 10.1007/s13258-022-01234-z (behind $40 paywall)
Biwei Cao # 1 2 3, Tao Wen # 1 2 3, Meng Wei 1 2 3, Yuan Xiong 1 2 3, Wan Liu 1 2 3, Li Zhu 1 2 3, Jing Zhou 4

Background: Vitamin D binding protein (VDBP) is an essential plasma carrier protein, which plays possible roles in reproductive health, disease and so on. However, the effects of VDBP on immunity have not been fully studied and the pertinent literatures remain very limited.

Objective: In this study, we introduced the exogenous VDBP into DC2.4 and established a stable DC2.4/VDBP cell line to explore the role of this gene in immunity.

Methods: Dendritic cells (DCs), as the most effective antigen presenting cells (APC) found so far, are directly involved in regulating some innate immunity. In order to evaluate the biological role of VDBP in DCs, we stably overexpressed VDBP in DCs, and conducted Cell Counting Kit-8 (CCK-8 kit) and flow cytometry to detect changes in cell function. CCK-8 kit was used to monitor the viability of DCs after gene overexpression, and flow cytometry was used to detect changes in cell cycle distribution and apoptosis. Subsequently, in order to reveal the mechanism of VDBP regulating DCs, we adopted RNA sequencing (RNA-seq).

Results: CCK-8 results revealed VDBP successfully inhibited viability of DCs. Besides, we found that overexpression of this gene greatly promoted apoptosis and obviously altered the cell cycle distribution of DCs in G1 and G2 phases. Moreover, RNA-seq was carried out and 151 differently expression genes (DEGs) were obtained. In addition, gene differential expression analysis showed that most of them were uniformly enriched in immunity-related pathways.

Conclusion: These results indicated that VDBP greatly repressed proliferation, facilitated apoptosis and changed cell cycle in DCs via altering the expression levels of gene associated with their cellular immunity.

References
  1. Akiba T, Morikawa T, Odaka M, Nakada T, Kamiya N, Yamashita M, Yabe M, Inagaki T, Asano H, Mori S et al (2018) Vitamin D supplementation and survival of patients with non-small cell lung cancer: a randomized, double-blind, placebo-controlled trial. Clin Cancer Res 24:4089–4097 - PubMed
  2. Bag AK, Saha S, Sundar S, Saha B, Chakrabarti A, Mandal C (2014) Comparative proteomics and glycoproteomics of plasma proteins in Indian visceral leishmaniasis. Proteome Sci 12:48 - PubMed - PMC
  3. Basatemur E, Horsfall L, Marston L, Rait G, Sutcliffe A (2017) Trends in the diagnosis of vitamin D deficiency. Pediatrics 139:3
  4. Behrouz GF, Farzaneh GS, Leila J, Jaleh Z, Eskandar KS (2013) Presence of auto-antibody against two placental proteins, annexin A1 and vitamin D binding protein, in sera of women with pre-eclampsia. J Reprod Immunol 99:10–16 - PubMed
  5. Berger D, Winter M, Beger HG (1990) Influence of human transferrin and group-specific protein on endotoxicity in vitro. Clin Chim Acta 189:1–5 - PubMed
  6. Binder R, Kress A, Kan G, Herrmann K, Kirschfink M (1999) Neutrophil priming by cytokines and vitamin D binding protein (Gc-globulin): impact on C5a-mediated chemotaxis, degranulation and respiratory burst. Mol Immunol 36:885–892 - PubMed
  7. Bouillon R, Schuit F, Antonio L, Rastinejad F (2019) Vitamin D binding protein: a historic overview. Front Endocrinol (lausanne) 10:910 PDF
  8. Braun A, Kofler A, Morawietz S, Cleve H (1993) Sequence and organization of the human vitamin D-binding protein gene. Biochim Biophys Acta 1216:385–394 - PubMed
  9. Briceno Noriega D, Savelkoul HFJ (2021) Vitamin D and allergy susceptibility during gestation and early life. Nutrients 13
  10. Carter CS, Kenkel WM, MacLean EL, Wilson SR, Perkeybile AM, Yee JR, Ferris CF, Nazarloo HP, Porges SW, Davis JM et al (2020) Is oxytocin “nature’s medicine”? Pharmacol Rev 72:829–861 - PubMed - PMC
  11. Cavanagh LL, Weninger W (2008) Dendritic cell behaviour in vivo: lessons learned from intravital two-photon microscopy. Immunol Cell Biol 86:428–438 - PubMed
  12. Cribbs AP, Kennedy A, Gregory B, Brennan FM (2013) Simplified production and concentration of lentiviral vectors to achieve high transduction in primary human T cells. BMC Biotechnol 13:98 - PubMed - PMC
  13. Dahl B, Schiodt FV, Ott P, Wians F, Lee WM, Balko J, O’Keefe GE (2003) Plasma concentration of Gc-globulin is associated with organ dysfunction and sepsis after injury. Crit Care Med 31:152–156 - PubMed
  14. de Menezes SL, Kelly JW, Wolfe R, Farrugia H, Mar VJ (2019) The increasing use of shave biopsy for diagnosing invasive melanoma in Australia. Med J Aust 211:213–218 - PubMed
  15. Delanghe JR, Speeckaert R, Speeckaert MM (2015) Behind the scenes of vitamin D binding protein: more than vitamin D binding. Best Pract Res Clin Endocrinol Metab 29:773–786 - PubMed
    Abstract Although being discovered in 1959, the number of published papers in recent years reveals that vitamin D binding protein (DBP), a member of the albuminoid superfamily, is a hot research topic. Besides the three major phenotypes (DBP1F, DBP1S and DBP2), more than 120 unique variants have been described of this polymorphic protein. The presence of DBP has been demonstrated in different body fluids (serum, urine, breast milk, ascitic fluid, cerebrospinal fluid, saliva and seminal fluid) and organs (brain, heart, lungs, kidneys, placenta, spleen, testes and uterus). Although the major function is binding, solubilization and transport of vitamin D and its metabolites, the name of this glycoprotein hides numerous other important biological functions. In this review, we will focus on the analytical aspects of the determination of DBP and discuss in detail the multifunctional capacity [actin scavenging, binding of fatty acids, chemotaxis, binding of endotoxins, influence on T cell response and influence of vitamin D binding protein-macrophage activating factor (DBP-MAF) on bone metabolism and cancer] of this abundant plasma protein.
  16. den Hartog G, van Altena C, Savelkoul HF, van Neerven RJ (2013) The mucosal factors retinoic acid and TGF-beta1 induce phenotypically and functionally distinct dendritic cell types. Int Arch Allergy Immunol 162:225–236
  17. Diaz-Ochoa VE, Jellbauer S, Klaus S, Raffatellu M (2014) Transition metal ions at the crossroads of mucosal immunity and microbial pathogenesis. Front Cell Infect Microbiol 4:2 - PubMed - PMC
  18. DiMartino SJ, Shah AB, Trujillo G, Kew RR (2001) Elastase controls the binding of the vitamin D-binding protein (Gc-globulin) to neutrophils: a potential role in the regulation of C5a co-chemotactic activity. J Immunol 166:2688–2694 - PubMed
  19. Dueland S, Nenseter MS, Drevon CA (1991) Uptake and degradation of filamentous actin and vitamin D-binding protein in the rat. Biochem J 274(Pt 1):237–241 - PubMed - PMC
  20. Faragher R, Frasca D, Remarque E, Pawelec G, ImAgin EC (2014) Better immunity in later life: a position paper. Age (dordr) 36:9619
  21. Fernando M, Ellery SJ, Marquina C, Lim S, Naderpoor N, Mousa A (2020) Vitamin D-binding protein in pregnancy and reproductive health. Nutrients 12:1489 - PMC
  22. Freire-Garabal M, Balboa JL, Nunez MJ, Castano MT, Llovo JB, Fernandez-Rial JC, Belmonte A (1991) Effects of amphetamine on T-cell immune response in mice. Life Sci 49:PL107–PL112 - PubMed
  23. Gasparri C, Curcio A, Torella D, Gaspari M, Celi V, Salituri F, Boncompagni D, Torella M, Gulletta E, Cuda G et al (2010) Proteomics reveals high levels of vitamin D binding protein in myocardial infarction. Front Biosci (elite Ed) 2:796–804
  24. Goodwin K, Nelson CM (2017) Generating tissue topology through remodeling of cell-cell adhesions. Exp Cell Res 358:45–51 - PubMed - PMC
  25. Govender P, Keyes CM, Hankinson EA, O’Hara CJ, Sanchorawala V, Berk JL (2017) Transbronchial biopsies safely diagnose amyloid lung disease. Amyloid 24:37–41 - PubMed - PMC
  26. Guha C, Osawa M, Werner PA, Galbraith RM, Paddock GV (1995) Regulation of human Gc (vitamin D-binding) protein levels: hormonal and cytokine control of gene expression in vitro. Hepatology 21:1675–1681 - PubMed
  27. Hiam-Galvez KJ, Allen BM, Spitzer MH (2021) Systemic immunity in cancer. Nat Rev Cancer 21:345–359 - PubMed - PMC
  28. Hoan NX, Tong HV, Song LH, Meyer CG, Velavan TP (2018) Vitamin D deficiency and hepatitis viruses-associated liver diseases: a literature review. World J Gastroenterol 24:445–460 - PubMed - PMC
  29. Honda T, Egawa G, Kabashima K (2019) Antigen presentation and adaptive immune responses in skin. Int Immunol 31:423–429 - PubMed
  30. Hong H, Wang Q, Li J, Liu H, Meng X, Zhang H (2019) Aging, cancer and immunity. J Cancer 10:3021–3027 - PubMed - PMC
  31. House RV, Thomas PT, Bhargava HN (1994) Comparison of immune functional parameters following in vitro exposure to natural and synthetic amphetamines. Immunopharmacol Immunotoxicol 16:1–21 - PubMed
  32. Kamel AM, Farid SF, Attia AS, El Raziky M (2017) Association of vitamin D binding protein polymorphisms with response to therapy in Egyptian chronic hepatitis C patients. J Infect Dev Countries 11:781–790
  33. Koike K, Shinozawa Y, Yamazaki M, Endo T, Nomura R, Aiboshi J, Samarghandian S, Emmett M, Peterson VM (2002) Recombinant human interleukin-1alpha increases serum albumin, Gc-globulin, and alpha1-antitrypsin levels in burned mice. Tohoku J Exp Med 198:23–29 - PubMed
  34. Kongsbak M, von Essen MR, Levring TB, Schjerling P, Woetmann A, Odum N, Bonefeld CM, Geisler C (2014) Vitamin D-binding protein controls T cell responses to vitamin D. BMC Immunol 15:35 - PubMed - PMC
  35. Li S, Wang F, Qu Y, Chen X, Gao M, Yang J, Zhang D, Zhang N, Li W, Liu H (2017) HDAC2 regulates cell proliferation, cell cycle progression and cell apoptosis in esophageal squamous cell carcinoma EC9706 cells. Oncol Lett 13:403–409 - PubMed
  36. Lind SE, Smith DB, Janmey PA, Stossel TP (1988) Depression of gelsolin levels and detection of gelsolin-actin complexes in plasma of patients with acute lung injury. Am Rev Respir Dis 138:429–434 - PubMed
  37. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408
  38. Mabbott NA, Bradford BM, Pal R, Young R, Donaldson DS (2020) The effects of immune system modulation on prion disease susceptibility and pathogenesis. Int J Mol Sci 21:7299 - PMC
  39. Michell DL, Vickers KC (2016) Lipoprotein carriers of microRNAs. Biochim Biophys Acta 1861:2069–2074 - PubMed - PMC
  40. Mirzakhani H, Al-Garawi A, Weiss ST, Litonjua AA (2015) Vitamin D and the development of allergic disease: how important is it? Clin Exp Allergy 45:114–125 - PubMed - PMC
  41. O’Garra A, Murphy K (1994) Role of cytokines in determining T-lymphocyte function. Curr Opin Immunol 6:458–466 - PubMed
  42. Onoe K, Yanagawa Y, Minami K, Iijima N, Iwabuchi K (2007) Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells. Immunol Res 38:319–332 - PubMed
  43. Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ (2003) The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 9:125–134 - PubMed - PMC
  44. Perez HD (1994) Gc globulin (vitamin D-binding protein) increases binding of low concentrations of C5a des Arg to human polymorphonuclear leukocytes: an explanation for its cochemotaxin activity. Inflammation 18:215–220 - PubMed
  45. Perez HD, Kelly E, Chenoweth D, Elfman F (1988) Identification of the C5a des Arg cochemotaxin. Homology with vitamin D-binding protein (group-specific component globulin). J Clin Invest 82:360–363 - PubMed - PMC
  46. Rani L, Minz RW, Arora A, Kannan M, Sharma A, Anand S, Gupta D, Panda NK, Sakhuja VK (2014) Serum proteomic profiling in granumomatosis with polyangiitis using two-dimensional gel electrophoresis along with matrix assisted laser desorption ionization time of flight mass spectrometry. Int J Rheum Dis 17:910–919 - PubMed
  47. Ravnsborg T, Olsen DT, Thysen AH, Christiansen M, Houen G, Hojrup P (2010) The glycosylation and characterization of the candidate Gc macrophage activating factor. Biochim Biophys Acta 1804:909–917 - PubMed
  48. Rozmus D, Ciesielska A, Plominski J, Grzybowski R, Fiedorowicz E, Kordulewska N, Savelkoul H, Kostyra E, Cieslinska A (2020) Vitamin D binding protein (VDBP) and its gene polymorphisms—the risk of malignant tumors and other diseases. Int J Mol Sci 21:7822 - PMC
  49. Schiodt FV, Ott P, Bondesen S, Tygstrup N (1997) Reduced serum Gc-globulin concentrations in patients with fulminant hepatic failure: association with multiple organ failure. Crit Care Med 25:1366–1370 - PubMed
  50. Sharifan P, Khoshakhlagh M, Khorasanchi Z, Darroudi S, Rezaie M, Safarian M, Vatanparast H, Afshari A, Ferns G, Ghazizadeh H et al (2020) Efficacy of low-fat milk and yogurt fortified with encapsulated vitamin D3 on improvement in symptoms of insomnia and quality of life: Evidence from the SUVINA trial. Food Sci Nutr 8:4484–4490 - PubMed - PMC
  51. Siddiqui M, Manansala JS, Abdulrahman HA, Nasrallah GK, Smatti MK, Younes N, Althani AA, Yassine HM (2020) Immune modulatory effects of vitamin D on viral infections. Nutrients 12:2879 - PMC
  52. Song YH, Naumova AK, Liebhaber SA, Cooke NE (1999) Physical and meiotic mapping of the region of human chromosome 4q11-q13 encompassing the vitamin D binding protein DBP/Gc-globulin and albumin multigene cluster. Genome Res 9:581–587 - PubMed - PMC
  53. Speeckaert MM, Wehlou C, De Somer F, Speeckaert R, Van Nooten GJ, Delanghe JR (2010) Evolution of vitamin D binding protein concentration in sera from cardiac surgery patients is determined by triglyceridemia. Clin Chem Lab Med 48:1345–1350 - PubMed
  54. Speeckaert MM, Speeckaert R, van Geel N, Delanghe JR (2014) Vitamin D binding protein: a multifunctional protein of clinical importance. Adv Clin Chem 63:1–57 - PubMed
  55. Thrailkill KM, Jo CH, Cockrell GE, Moreau CS, Fowlkes JL (2011) Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency? J Clin Endocrinol Metab 96:142–149 - PubMed
  56. Trapnell C, Pachter L, Salzberg SL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25:1105–1111 - PubMed - PMC
  57. Trujillo G, Zhang J, Habiel DM, Ge L, Ramadass M, Ghebrehiwet B, Kew RR (2011) Cofactor regulation of C5a chemotactic activity in physiological fluids. Requirement for the vitamin D binding protein, thrombospondin-1 and its receptors. Mol Immunol 49:495–503 - PubMed - PMC
  58. Trujillo G, Habiel DM, Ge L, Ramadass M, Cooke NE, Kew RR (2013) Neutrophil recruitment to the lung in both C5a- and CXCL1-induced alveolitis is impaired in vitamin D-binding protein-deficient mice. J Immunol 191:848–856 - PubMed
  59. Turner AM, McGowan L, Millen A, Rajesh P, Webster C, Langman G, Rock G, Tachibana I, Tomlinson MG, Berditchevski F et al (2013) Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology. Eur Respir J 41:410–416 - PubMed
  60. Wang H, Cheng B, Chen Q, Wu S, Lv C, Xie G, Jin Y, Fang X (2008) Time course of plasma gelsolin concentrations during severe sepsis in critically ill surgical patients. Crit Care 12:R106 - PubMed - PMC
  61. Wang B, Li Y, Shao C, Tan Y, Cai L (2012) Cadmium and its epigenetic effects. Curr Med Chem 19:2611–2620 - PubMed
  62. Wang Y, Cui ZQ, Luo TB, Liu L (2016) Correlations of VDR and VDBP genetic polymorphisms with susceptibility to adolescent idiopathic scoliosis and efficacy of brace treatment. Genomics 108:194–200 - PubMed
  63. Wang M, Yu X, Yang Y (2020) Diagnosing kikuchi’s disease on fine needle aspiration biopsy. Cytopathology 31:22–25 - PubMed
  64. Wang M, Zhou T, Li X, Ma H, Liang Z, Fonseca VA, Heianza Y, Qi L (2020b) Baseline vitamin D status, sleep patterns, and the risk of incident type 2 diabetes in data from the UK biobank study. Diabetes Care 43:2776–2784 - PubMed - PMC
  65. Wang W, Hu W, Xue S, Chen Q, Jiang Y, Zhang H, Zuo W (2021) Vitamin D and lung cancer; association, prevention, and treatment. Nutr Cancer 73:2188–2200
  66. Watt GH, Ashton SH, Cook JA, Wise WC, Halushka PV, Galbraith RM (1989) Alterations in plasma levels and complexing of Gc (vitamin D-binding protein) in rats with endotoxic shock. Circ Shock 28:279–291 - PubMed
  67. Yang M, Wang S, Wang S, Ma J, Xu X, Mao C, Ma B, Tong J, Qiu G, Shao Q et al (2008) Tat-mediated intracellular delivery of T-bet protein into THP-1 cells can induce Th1-type response. Immunol Invest 37:97–111 - PubMed
  68. Yang R, Broussard JA, Green KJ, Espinosa HD (2018) Techniques to stimulate and interrogate cell-cell adhesion mechanics. Extreme Mech Lett 20:125–139 - PubMed
  69. Zanoni P, Velagapudi S, Yalcinkaya M, Rohrer L, von Eckardstein A (2018) Endocytosis of lipoproteins. Atherosclerosis 275:273–295 - PubMed
  70. Zhang Y, Ma Z, Wang Y, Boyer J, Ni G, Cheng L, Su S, Zhang Z, Zhu Z, Qian J et al (2020) Streptavidin promotes DNA binding and activation of cGAS to enhance innate immunity. iScience 23:101463 - PubMed - PMC
  71. Zhu J, Petit PF, Van den Eynde BJ (2019) Apoptosis of tumor-infiltrating T lymphocytes: a new immune checkpoint mechanism. Cancer Immunol Immunother 68:835–847 - PubMed

VitaminDWIKi - Vitamin D Binding Protein category listing has 177 items and the following:

Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,

  • GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
  • The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
  • The actual D getting to the cells is a function of measured D and all 4 genes
  • There is >2X increase in 8+ health problems if have poor VDBP (GC)
  • It appears that VDBP only blocks oral vitamin D,

VitaminDWIKi - Vitamin D Binding Protein has

Increased
Risk		Health Problem
11 XPreeclampsia
6.5XT1D in SA Blacks
6 XFood Allergy
5 XPTSD
4 X, 5XKidney Cancer
4 XPoor Response to Oral Vitamin D
3 XEar infection
2.8 X MS
2 X Colorectal Cancer
2 XProstate Cancer -in those with dark skins
1.3 XInfertility

VitaminDWIKi - Additional information on Genetics

Gene# of pages Location
CYP27A1449 (Sept 2019) Liver
*CYP2R1826 (Sept 2019)Liver & Tissue
CYP27B11430   (Sept 2019) Kidney & Tissue
CYP24A128 in title - May 2022] excrete excess
Created by admin. Last Modification: Sunday March 13, 2022 14:35:01 GMT-0000 by admin. (Version 7)
Vitamin D Binding Protein may affect immune system dendritic cells – March 2022        
2612 visitors, last modified 13 Mar, 2022,
Printer Friendly Follow this page for updates
Immunity 248 Vit D Binding Protein 173
Page actions
Print
Edit Files 1