The lungs can activate vitamin D locally – a Vitamin D inhaler may help lungs – Aug 2016

---

VITAMIN D EFFECTS ON LUNG IMMUNITY AND RESPIRATORY DISEASES

Vitam Horm. 2011 ; 86: 217-237. doi:10.1016/B978-0-12-386960-9.00009-5.
Sif Hansdottir, MD, MS and Martha M. Monick, Ph.D.
Dept of Medicine, University of Iowa Carver College of Medicine and Veterans Administration Medical Center, Iowa City, IA 52242

 Download the PDF from VitaminDWiki

SUMMARY
Our understanding of vitamin D metabolism and biological effects has grown exponentially in recent years and it has become clear that vitamin D has extensive immunomodulatory effects.
The active vitamin D generating enzyme, 1a-hydroxylase, is expressed by the airway epithelium, alveolar macrophages, dendritic cells and lymphocytes indicating that active vitamin D can be produced locally within the lungs.
Vitamin D generated in tissues is responsible for many of the immunomodulatory actions of vitamin D.
The effects of vitamin D within the lungs include increased secretion of the antimicrobial peptide cathelicidin, decreased chemokine production, inhibition of dendritic cell activation and alteration of T cell activation. These cellular effects are important for host responses against infection and the development of allergic lung diseases like asthma. Epidemiological studies do suggest that vitamin D deficiency predisposes to viral respiratory tract infections and mycobacterial infections and that vitamin D may play a role in the development and treatment of asthma. Randomized, placebo controlled trials are lacking but ongoing.

Section from the PDF

III. 1,25-DIHYDROXYVITAMIN D IS GENERATED LOCALLY IN THE LUNGS

Humans get vitamin D through synthesis in the skin following UVB exposure and to a lesser extent from limited dietary sources. Vitamin D from the skin or diet is metabolized primarily in the liver to 25-hydroxyvitamin D3 (25D) (Ponchon, Kennan et al. 1969). 25Dis the “storage form” of vitamin D and is used to determine the vitamin D status of individuals.

The last and rate limiting step in the synthesis of “active” 1,25-dihydroxyvitamin D3 (1,25D) is catalyzed by the mitochondrial enzyme 1a-hydroxylase and is conventionally known to take place in the kidneys. Renal 1a-hydroxylase activity is under stringent regulation by parathyroid hormone, calcium, calcitonin, phosphorus and 1,25D itself (ZEHNDER, BLAND et al. 1999). Vitamin D is inactivated by the ubiquitous enzyme, 24- hydroxylase, whose expression is inducible by 1,25D, thus creating a negative feedback loop (Holick 2007). The biological effects of vitamin D are achieved through the regulation of gene expression mediated by the vitamin D receptor (VDR) (Baker, McDonnell et al. 1988). Active vitamin D binds to VDR and upon ligand binding, the receptor dimerizes with the retinoic X receptor (RXR) (MacDonald, Dowd et al. 1993). The VDR/RXR complex binds to vitamin D responsive elements (VDREs) within the promoter regions of vitamin D regulated genes (Sutton and MacDonald 2003).
It is increasingly recognized that localized synthesis of 1,25D rather than systemic production is responsible for many of the immune effects of vitamin D. Extra-renal expression of 1a-hydroxylase has been found in various cells of the immune system including alveolar macrophages (Adams, Sharma et al. 1983; Reichel, Koeffler et al. 1987), dendritic cells (Fritsche, Mondal et al. 2003; Hewison, Freeman et al. 2003; Sigmundsdottir, Pan et al. 2007) and lymphocytes (Chen, Sims et al. 2007; Sigmundsdottir, Pan et al. 2007) as well as in airway epithelia (Hansdottir, Monick et al. 2008) (Table 1). Locally formed 1,25D acts in an autocrine or paracrine fashion to modulate cell proliferation, cell differentiation and immune function (Bell 1998; Hewison, Burke et al. 2007; White 2008).

---

See also web

• Respiratory Epithelial Cells Convert Inactive Vitamin D to its Active Form Nov 2009 Full text online
• Active form of vitamin D actually counteracts the effects of cigarette smoke in the lab - March 2015

1α, 25-hydroxy vitamin D3 counteracts the effects of cigarette smoke in airway epithelial cells
Cellular Immunology, doi:10.1016/j.cellimm.2015.03.004
Ruhui Zhanga, Haijin Zhaoa, Hangming Donga, Fei Zoub, Shaoxi Caia, ,
a Department of Respiratory, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
b School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China

Cigarette smoke extracts (CSE) alter calpain-1 expression via ERK signaling pathway in bronchial epithelial cells. 1α,25-dihydroxyvitamin D3 (1,25D3) inhibits cigarette smoke-induced epithelial barrier disruption.

This study was aimed to explore whether the 1,25D3 counteracted the CSE effects in a human bronchial epithelial cell line (16HBE). In particular, transepithelial electrical resistance (TER) and permeability, expression and distribution of E-cadherin and β-catenin, calpain-1 expression, and ERK phosphorylation were assessed in the CSE-stimulated 16HBE cells. The CSE induced the ERK phosphorylation, improved the calpain-1 expression, increased the distribution anomalies and the cleaving of E-cadherin and β-catenin, and resulted in the TER reduction and the permeability increase. The 1,25D3 reduced these pathological changes. The 1,25D3 mediated effects were associated with a reduced ERK phosphorylation.

In conclusion, the present study provides compelling evidences that the 1,25D3 may be considered a possible valid therapeutic option in controlling the cigarette smoke-induced epithelial barrier disruption.

PDF is available free at Sci-Hub   10.1016/j.cellimm.2015.03.004

---

Intranasal emulsions (Vitamin D in the future?)

• in VitaminDWiki Nasal Vitamin B12 treatment for children (perhaps nasal Vitamin D too) – Nov 2019
• C. V. Pardeshi and V. S. Belgamwar, “Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: An excellent platform for brain targeting,” Expert Opinion on Drug Delivery, vol. 10, no. 7, pp. 957–972, 2013.
• W.-Y. Ong, S.-M. Shalini, and L. Costantino, “Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders,” Current Medicinal Chemistry, vol. 21, no. 37, pp. 4247–4256, 2014.
• L. Illum, “Nasal drug delivery—possibilities, problems and solutions,” Journal of Controlled Release, vol. 87, no. 1-3, pp. 187–198, 2003.
• P. Khadka, J. Ro, H. Kim et al., “Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability,” Asian Journal of Pharmaceutical Sciences, vol. 9, no. 6, pp. 304–316, 2014.
• V. Puri, “A study on nano emulsion (Emulgel),” International Journal of Advanced Pharmaceutical Sciences, vol. 1, no. 3, pp. 27–55, 2018

Short URL = is.gd/Inhale1

---

There have been 33047 visits to this page