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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

General Research Article

Increased Circulatory Extrarenal 1α,25-Dihydroxyvitamin D3 in Bilaterally Nephrectomized Rats

Author(s): Murat Dabak*, Durrin O. Dabak, Tuncay Kuloglu, Ersoy Baydar, Hakan Bulut and Ozgur Ozoner

Volume 20, Issue 9, 2020

Page: [1523 - 1530] Pages: 8

DOI: 10.2174/1871530320666200530222426

Price: $65

Abstract

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown.

Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS).

Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis.

Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D.

Conclusion: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.

Keywords: , 25-dihydroxyvitamin D3, 25-hydroxyvitamin D, inflammation, extrarenal, anephric, rat.

Graphical Abstract

[1]
Adams, J.S.; Hewison, M. Update in vitamin D. J. Clin. Endocrinol. Metab., 2010, 95(2), 471-478.
[http://dx.doi.org/10.1210/jc.2009-1773 ] [PMID: 20133466]
[2]
Holick, M.F.; MacLaughlin, J.A.; Clark, M.B.; Holick, S.A.; Potts, J.T., Jr; Anderson, R.R.; Blank, I.H.; Parrish, J.A.; Elias, P. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science, 1980, 210(4466), 203-205.
[http://dx.doi.org/10.1126/science.6251551 ] [PMID: 6251551]
[3]
Adams, J.S.; Hewison, M. Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch. Biochem. Biophys., 2012, 523(1), 95-102.
[http://dx.doi.org/10.1016/j.abb.2012.02.016 ] [PMID: 22446158]
[4]
Bikle, D.D. Vitamin D metabolism, mechanism of action, and clinical applications. Chem. Biol., 2014, 21(3), 319-329.
[http://dx.doi.org/10.1016/j.chembiol.2013.12.016 ] [PMID: 24529992]
[5]
Chen, S.; Sims, G.P.; Chen, X.X.; Gu, Y.Y.; Chen, S.; Lipsky, P.E. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J. Immunol., 2007, 179(3), 1634-1647.
[http://dx.doi.org/10.4049/jimmunol.179.3.1634 ] [PMID: 17641030]
[6]
Monkawa, T.; Yoshida, T.; Hayashi, M.; Saruta, T. Identification of 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression in macrophages. Kidney Int., 2000, 58(2), 559-568.
[http://dx.doi.org/10.1046/j.1523-1755.2000.00202.x ] [PMID: 10916079]
[7]
Sigmundsdottir, H.; Pan, J.; Debes, G.F.; Alt, C.; Habtezion, A.; Soler, D.; Butcher, E.C. DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat. Immunol., 2007, 8(3), 285-293.
[http://dx.doi.org/10.1038/ni1433 ] [PMID: 17259988]
[8]
Yip, K.H.; Kolesnikoff, N.; Yu, C.; Hauschild, N.; Taing, H.; Biggs, L.; Goltzman, D.; Gregory, P.A.; Anderson, P.H.; Samuel, M.S.; Galli, S.J.; Lopez, A.F.; Grimbaldeston, M.A. Mechanisms of vitamin D metabolite repression of IgE-dependent mast cell activation J. Allergy Clin. Immunol., 2014.133(5), 1356-1364, 1364.e1-1364.e14..
[http://dx.doi.org/10.1016/j.jaci.2013.11.030] [PMID: 24461581]
[9]
Kreutz, M.; Andreesen, R.; Krause, S.W.; Szabo, A.; Ritz, E.; Reichel, H. 1,25-dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages. Blood, 1993, 82(4), 1300-1307.
[http://dx.doi.org/10.1182/blood.V82.4.1300.1300 ] [PMID: 8394753]
[10]
Brennan, A.; Katz, D.R.; Nunn, J.D.; Barker, S.; Hewison, M.; Fraher, L.J.; O’Riordan, J.L. Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol. Immunology, 1987, 61(4), 457-461.
[PMID: 2832307]
[11]
Bhalla, A.K.; Amento, E.P.; Clemens, T.L.; Holick, M.F.; Krane, S.M. Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J. Clin. Endocrinol. Metab., 1983, 57(6), 1308-1310.
[http://dx.doi.org/10.1210/jcem-57-6-1308 ] [PMID: 6313738]
[12]
Takahashi, K.; Nakayama, Y.; Horiuchi, H.; Ohta, T.; Komoriya, K.; Ohmori, H.; Kamimura, T. Human neutrophils express messenger RNA of vitamin D receptor and respond to 1alpha,25-dihydroxyvitamin D3. Immunopharmacol. Immunotoxicol., 2002, 24(3), 335-347.
[http://dx.doi.org/10.1081/IPH-120014721 ] [PMID: 12375732]
[13]
Baeke, F.; Korf, H.; Overbergh, L.; van Etten, E.; Verstuyf, A.; Gysemans, C.; Mathieu, C. Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system. J. Steroid Biochem. Mol. Biol., 2010, 121(1-2), 221-227.
[http://dx.doi.org/10.1016/j.jsbmb.2010.03.037 ] [PMID: 20302932]
[14]
Provvedini, D.M.; Tsoukas, C.D.; Deftos, L.J.; Manolagas, S.C. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science, 1983, 221(4616), 1181-1183.
[http://dx.doi.org/10.1126/science.6310748 ] [PMID: 6310748]
[15]
Baeke, F.; Takiishi, T.; Korf, H.; Gysemans, C.; Mathieu, C.; Vitamin, D.; Vitamin, D. Modulator of the immune system. Curr. Opin. Pharmacol., 2010, 10(4), 482-496.
[http://dx.doi.org/10.1016/j.coph.2010.04.001 ] [PMID: 20427238]
[16]
Adams, J.S.; Singer, F.R.; Gacad, M.A.; Sharma, O.P.; Hayes, M.J.; Vouros, P.; Holick, M.F. Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. J. Clin. Endocrinol. Metab., 1985, 60(5), 960-966.
[http://dx.doi.org/10.1210/jcem-60-5-960 ] [PMID: 2984238]
[17]
Reichel, H.; Koeffler, H.P.; Barbers, R.; Norman, A.W. Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. J. Clin. Endocrinol. Metab., 1987, 65(6), 1201-1209.
[http://dx.doi.org/10.1210/jcem-65-6-1201 ] [PMID: 3119653]
[18]
Lagishetty, V.; Chun, R.F.; Liu, N.Q.; Lisse, T.S.; Adams, J.S.; Hewison, M. 1alpha-hydroxylase and innate immune responses to 25-hydroxyvitamin D in colonic cell lines. J. Steroid Biochem. Mol. Biol., 2010, 121(1-2), 228-233.
[http://dx.doi.org/10.1016/j.jsbmb.2010.02.004 ] [PMID: 20152900]
[19]
Barbour, G.L.; Coburn, J.W.; Slatopolsky, E.; Norman, A.W.; Horst, R.L. Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D. N. Engl. J. Med., 1981, 305(8), 440-443.
[http://dx.doi.org/10.1056/NEJM198108203050807 ] [PMID: 6894783]
[20]
D’Aurizio, F.; Villalta, D.; Metus, P.; Doretto, P.; Tozzoli, R. Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases? Autoimmun. Rev., 2015, 14(5), 363-369.
[http://dx.doi.org/10.1016/j.autrev.2014.10.008 ] [PMID: 25308530]
[21]
Adams, J.S.; Gacad, M.A. Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis. J. Exp. Med., 1985, 161(4), 755-765.
[http://dx.doi.org/10.1084/jem.161.4.755 ] [PMID: 3838552]
[22]
Abreu, M.T.; Kantorovich, V.; Vasiliauskas, E.A.; Gruntmanis, U.; Matuk, R.; Daigle, K.; Chen, S.; Zehnder, D.; Lin, Y.C.; Yang, H.; Hewison, M.; Adams, J.S. Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn’s disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Gut, 2004, 53(8), 1129-1136.
[http://dx.doi.org/10.1136/gut.2003.036657 ] [PMID: 15247180]
[23]
Blaney, G.P.; Albert, P.J.; Proal, A.D. Vitamin D metabolites as clinical markers in autoimmune and chronic disease. Ann. N. Y. Acad. Sci., 2009, 1173, 384-390.
[http://dx.doi.org/10.1111/j.1749-6632.2009.04875.x ] [PMID: 19758177]
[24]
Dabak, M.; Dabak, D.O.; Karapinar, T.; Bulut, H. Vitamin D status in cattle with malignant catarrhal fever. J. Vet. Med. Sci., 2012, 74(1), 125-128.
[http://dx.doi.org/10.1292/jvms.11-0303 ] [PMID: 21891975]
[25]
Holick, M.F. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am. J. Clin. Nutr., 2004, 80(Suppl. 6), 1678S-1688S.
[http://dx.doi.org/10.1093/ajcn/80.6.1678S ] [PMID: 15585788]
[26]
Brandi, L.; Egfjord, M.; Olgaard, K. Pharmacokinetics of 1,25(OH)(2)D(3) and 1α(OH)D(3) in normal and uraemic men. Nephrol. Dial. Transplant., 2002, 17(5), 829-842.
[http://dx.doi.org/10.1093/ndt/17.5.829 ] [PMID: 11981071]
[27]
Kissmeyer, A.M.; Binderup, L. Calcipotriol (MC 903): pharmacokinetics in rats and biological activities of metabolites. A comparative study with 1,25(OH)2D3. Biochem. Pharmacol., 1991, 41(11), 1601-1606.
[http://dx.doi.org/10.1016/0006-2952(91)90160-7 ] [PMID: 2043150]
[28]
Dusso, A.S.; Negrea, L.; Gunawardhana, S.; Lopez-Hilker, S.; Finch, J.; Mori, T.; Nishii, Y.; Slatopolsky, E.; Brown, A.J. On the mechanisms for the selective action of vitamin D analogs. Endocrinology, 1991, 128(4), 1687-1692.
[http://dx.doi.org/10.1210/endo-128-4-1687 ] [PMID: 2004595]
[29]
Freundlich, M.; Zilleruelo, G.; Strauss, J. Acute Renal Disorders and Renal Emergencies; Martinus Nijhoff Publishing: Boston, 1984.
[30]
Somerville, P.J.; Kaye, M. Resistance to parathyroid hormone in renal failure: Role of vitamin D metabolites. Kidney Int., 1978, 14(3), 245-254.
[http://dx.doi.org/10.1038/ki.1978.116 ] [PMID: 723151]
[31]
Galceran, T.; Martin, K.J.; Morrissey, J.J.; Slatopolsky, E. Role of 1,25-dihydroxyvitamin D on the skeletal resistance to parathyroid hormone. Kidney Int., 1987, 32(6), 801-807.
[http://dx.doi.org/10.1038/ki.1987.279 ] [PMID: 3430963]
[32]
Massry, S.G.; Stein, R.; Garty, J.; Arieff, A.I.; Coburn, J.W.; Norman, A.W.; Friedler, R.M. Skeletal resistance to the calcemic action of parathyroid hormone in uremia: Role of 1,25 (OH)2 D3. Kidney Int., 1976, 9(6), 467-474.
[http://dx.doi.org/10.1038/ki.1976.60 ] [PMID: 940279]

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