(June 18, 2011) — Laboratory-grown gingival cells treated with vitamin D boosted their production of an endogenous antibiotic, and killed more bacteria than untreated cells, according to a paper in the June 2011 issue of the journal Infection and Immunity. The research suggests that vitamin D can help protect the gums from bacterial infections that lead to gingivitis and periodontitis. Periodontitis affects up to 50 percent of the US population, is a major cause of tooth loss, and can also contribute to heart disease. Most Americans are deficient in vitamin D.
His interest piqued by another laboratory's discovery that vitamin D could stimulate white blood cells to produce natural proteins that have antibiotic activity, Gill Diamond of the UMDNJ — New Jersey Dental School, Newark, showed that vitamin D could stimulate lung cells to produce LL-37, a natural antibiotic protein, and kill more bacteria.
That suggested that , vitamin D might help cystic fibrosis patients. Next, in the new research, he showed that vitamin D has the same effct on gingival cells.
Then, Diamond found that vitamin D also stimulates gingival cells to produce another protein, called TREM-1, which had not been well-studied, but which was thought to be made by white blood cells. He found that it boosts production of pro-inflammatory cytokines.
The new research also showed that vitamin D coordinates expression of a number of genes not previously considered to be part of the vitamin D pathway. Those genes may be involved in additional infection-fighting pathways. A more comprehensive understanding of how vitamin D carries out this regulation at the molecular level — something Diamond hopes to investigate — will enable targeted therapies using vitamin D, he says.
Interestingly, Diamond also found that lung and gum cells appear to have the ability to activate inactive forms of vitamin D, says Diamond. "This means that we may even be able to use vitamin D therapy topically, if that proves true."
Vitamin D has become a hot area of research in recent years. In addition to infectious diseases, studies suggest that it has protective effects against autoimmune diseases, and certain cancers.
Diamond says that after he began conducting research on vitamin D, he began taking it as a supplement. Since then, "I have had only one cold in four years, and that one lasted only three days," he says. "Other people I've met who have done the same have seen similar results. We are trying to figure out how it's working, and what other infectious diseases can be mitigated by it.”
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Infect Immun. 2011 Jun;79(6):2250-6. Epub 2011 Mar 21.
McMahon L, Schwartz K, Yilmaz O, Brown E, Ryan LK, Diamond G.
Department of Oral Biology, UMDNJ-New Jersey Dental School, 185 South Orange Ave., Newark, NJ 07101. gdiamond at umdnj.edu.
Human gingival epithelial cells (GEC) produce peptides, such as ?-defensins and the cathelicidin LL-37, that are both antimicrobial and that modulate the innate immune response. In myeloid and airway epithelial cells, the active form of vitamin D(3) 1,25(OH)(2)D(3) increases the expression and antibacterial activity of LL-37. To examine the activity of vitamin D on the innate immune defense of the gingival epithelium, cultured epithelial cells were treated with either 10(-8) M 1,25(OH)(2)D(3) or ethanol for up to 24 h. A time-dependent induction of LL-37 mRNA up to 13-fold at 24 h in both standard monolayer and three-dimensional cultures was observed. Induction of the vitamin D receptor and the 1-?-hydroxylase genes was also observed. The hydroxylase was functional, as LL-37 induction was observed in response to stimulation by 25(OH)D(3). Through microarray analysis of other innate immune genes, CD14 expression increased 4-fold, and triggering receptor expressed on myeloid cells-1 (TREM-1) was upregulated 16-fold after 24 h of treatment with 1,25(OH)(2)D(3). TREM-1 is a pivotal amplifier of the innate immune response in macrophages, leading to increased production by inflammatory response genes. Activation of TREM-1 on the GEC led to an increase in interleukin-8 (IL-8) mRNA levels. Incubation of three-dimensional cultures with 1,25(OH)(2)D(3) led to an increase in antibacterial activity against the periodontal pathogen Aggregatibacter actinomycetemcomitans when the bacteria were added to the apical surface. This study is the first to demonstrate the effect of vitamin D on antibacterial defense of oral epithelial cells, suggesting that vitamin D(3) could be utilized to enhance the innate immune defense in the oral cavity.
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