Direct and Indirect Induction by 1,25-Dihydroxyvitamin D3 of the NOD2/CARD15-Defensin β2 Innate Immune Pathway Defective in Crohn Disease

Wang, Tiantian; Dabbas, Basel; Laperrière, David; Bitton, Ari J.; Soualhine, Hafid; Tavera-Mendoza, Luz E.; Dionne, Serge; Servant, Marc J.; Bitton, Alain; Seidman, Ernest G.; Mader, Sylvie; Behr, Marcel A.; White, John H.

doi:10.1074/jbc.c109.071225

Cited by 352 publications

(306 citation statements)

References 38 publications

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“…In addition, vitamin D deficiency [174], as well as active and passive tobacco smoking [13,175], air pollution [176] or improved domestic hygiene and sanitation [177] are additional factors that may modify the homeostasis of the intestinal mucosa. The observations, that IBD is common in Western countries, while uncommon in less developed areas, raised the intriguing hypothesis that improved hygiene and the consequent loss of routine exposure to parasitic worms (helminths) may play an important role in the pathomechanism of IBD [178].…”

Section: Environmental Factorsmentioning

confidence: 99%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e.g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN--1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.

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Section: Environmental Factorsmentioning

confidence: 99%

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gyires¹,

Tóth²,

Zádori

2014

CPD

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“…Indeed, Kanchwala et al showed that patients with sarcoidosis expressed the antimicrobial peptide cathelicidin less than healthy subjects, and that the sickest sarcoidosis patients expressed it least of all. 51 In patients with Crohn's disease, Wang et al also demonstrated a decline in levels of cathelicidin, 52 while Wiken et al showed reduced TLR2 mRNA expression in patients with Lofgren's syndrome. 53 After a certain level of dysbiosis has occurred, people may well reach the point where they can be diagnosed with an autoimmune/inflammatory condition.…”

Section: Successive Infectionmentioning

confidence: 99%

Immunostimulation in the era of the metagenome

Proal

Albert

Blaney³

et al. 2011

Cell Mol Immunol

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Microbes are increasingly being implicated in autoimmune disease. This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated. The standard of care for autoimmune disease remains the use of medications that slow the immune response, while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response. Immunostimulation is complicated by a cascade of sequelae, including exacerbated inflammation, which occurs in response to microbial death. Over the past 8 years, we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease. This intervention, designed to stimulate the innate immune response, has required a reevaluation of disease progression and amelioration. Paramount is the inherent conflict between palliation and microbicidal efficacy. Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms. Further studies are needed, but they will require careful planning to manage this immunopathology.

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“…IL-1β has been implicated in the pathogenesis of human cerebral malaria and severe malaria anemia [86][87]. However, calcitriol strongly stimulates NOD2 expression in differentiated human THP-1 macrophage-like cells, primary human monocytes and keratinocytes [88], and boosts autophagy by enhancing NOD2 function [89]. The calcitriol-stimulated NOD2 function may contribute to host resistance to a variety of infectious challenges.…”

Section: The Genomic Factors Associated With Vitamin D In Malariamentioning

confidence: 99%

The role of Vitamin D in malaria

Lương

Nguyễn

2015

J Infect Dev Ctries

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An abnormal calcium-parathyroid hormone (PTH)-vitamin D axis has been reported in patients with malaria infection. A role for vitamin D in malaria has been suggested by many studies. Genetic studies have identified numerous factors that link vitamin D to malaria, including human leukocyte antigen genes, toll-like receptors, heme oxygenase-1, angiopoietin-2, cytotoxic T lymphocyte antigen-4, nucleotide-binding oligomerization domain-like receptors, and Bcl-2. Vitamin D has also been implicated in malaria via its effects on the Bacillus CalmetteGuerin (BCG) vaccine, matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, reactive oxidative species, and nitric oxide synthase. Vitamin D may be important in malaria; therefore, additional research on its role in malaria is needed.

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Direct and Indirect Induction by 1,25-Dihydroxyvitamin D3 of the NOD2/CARD15-Defensin β2 Innate Immune Pathway Defective in Crohn Disease

Cited by 352 publications

References 38 publications

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

Immunostimulation in the era of the metagenome

The role of Vitamin D in malaria

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