1α,25-dihydroxyvitamin D3 a nd 19-nor-1α,25-dihydroxyvitamin 32 suppress immunoglobulin production and thymic lymphocyte proliferation in vivo

Yang, Shouli; Smith, Connie; DeLuca, Hector F.

doi:10.1016/0304-4165(93)90026-5

Cited by 60 publications

(33 citation statements)

References 27 publications

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“…59 Furthermore, calcitriol controls the growth of melanoma cells, [60][61][62] inhibits tumor promotion 63 and angiogenesis, 64 and boosts the immune system. [65][66][67] Recently, the importance of vitamin D in T cell activation has been revealed; they cannot kill virally infected cells or cancer cells unless they have enough vitamin D. 65 Other than our data suggesting low vitamin D 3 levels as one of 2 major risk factors for getting CMM, we believe the other major risk factor is HPV infection. Although we do not present any data to support our belief, we think HPV is involved because HPV-38 is found in over half the CMM biopsies [35][36][37][38] and HPV infection is increasing at an exponential rate in Europe.…”

Section: Discussionmentioning

confidence: 62%

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

Merrill

Ashrafi

Subramanian

et al. 2015

Dermato-Endocrinology

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(2015) Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors, Dermato-Endocrinology, 7:1, e1004018, DOI: 10.1080DOI: 10. /19381980.2014 For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find b HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D 3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D 3 and possibly viral infection.

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Section: Discussionmentioning

confidence: 62%

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

Merrill

Ashrafi

Subramanian

et al. 2015

Dermato-Endocrinology

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“…The physiological role of vitamin D in immune responses is not clearly defined. In vivo, both an excess and a deficiency of vitamin D suppress the delayed hypersensitivity response (66) or Ig production (67). Vitamin D-deficient animals and humans have a higher risk of infection, probably related to impaired macrophage function (68).…”

Section: Effects Of 1␣25-(oh) 2 D 3 On Already Differentiated Immatumentioning

confidence: 99%

Vitamin D3 Affects Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

Piemonti

Monti

Sironi

et al. 2000

The Journal of Immunology

561

419

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We studied the effects of 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) on differentiation, maturation, and functions of dendritic cells (DC) differentiated from human monocytes in vitro in the presence of GM-CSF and IL-4 for 7 days. Recovery and morphology were not affected by 1α,25-(OH)2D3 up to 100 nM. DC differentiated in the presence of 10 nM 1α,25-(OH)2D3 (D3-DC) showed a marked decrease in the expression of CD1a, while CD14 remained elevated. Mannose receptor and CD32 were significantly increased, and this correlated with an enhancement of endocytic activity. Costimulatory molecules such as CD40 and CD86 were slightly decreased or nonsignificantly affected (CD80 and MHC II). However, after induction of DC maturation with LPS or incubation with CD40 ligand-transfected cells, D3-DC showed marginal increases in MHC I, MHC II, CD80, CD86, CD40, and CD83. The accessory cell function of D3-DC in classical MLR was also inhibited. Moreover, allogeneic T cells stimulated with D3-DC were poor responders in a second MLR to untreated DC from the same or an unrelated donor, thus indicating the onset of a nonspecific hyporesponsivity. In conclusion, our data suggest that 1α,25-(OH)2D3 may modulate the immune system, acting at the very first step of the immune response through the inhibition of DC differentiation and maturation into potent APC.

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“…It has been demonstrated that the delayed hypersensitivity response to dinitrobenzene is impaired in vitamin D deficient mice (92), which tends to confirm the modulator control of 1,25-(OH) 2 D 3 in T cell-mediated immunity. The T-cell immune response depending on D hormone levels displays a characteristic inverted "U" curve (93). While this field requires more research investment, this particular activity of D-hormone analogs is the rationale for studies and trials on alfacalcidol and calcitriol for treating autoimmune disorders, including RA.…”

Section: Immunological Role Of Alfacalcidol (Fig 4)mentioning

confidence: 99%

D-Hormone analog alfacalcidol: an update on its role in post-menopausal osteoporosis and rheumatoid arthritis management

et al. 2005

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1α,25-dihydroxyvitamin D3 a nd 19-nor-1α,25-dihydroxyvitamin 32 suppress immunoglobulin production and thymic lymphocyte proliferation in vivo

Cited by 60 publications

References 27 publications

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

Vitamin D3 Affects Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

D-Hormone analog alfacalcidol: an update on its role in post-menopausal osteoporosis and rheumatoid arthritis management

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