Vitamin D3 Induces Autophagy in Human Monocytes/Macrophages via Cathelicidin

Yuk, Jae–Min; Shin, Dong–Min; Lee, Hyemi; Yang, Chul–Su; Jin, Hyo Sun; Kim, Kwang–Kyu; Lee, Zee-Won; Lee, Sang‐Hee; Kim, Jin Man; Jo, Eun-Kyeong

doi:10.1016/j.chom.2009.08.004

Cited by 703 publications

(692 citation statements)

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“…7 Vitamin D exerts its effects on innate immune responses by the promotion of autophagy and the suppression of tissue remodeling and lung matrix breakdown. 8,9 A systematic review and meta-analysis on low serum vitamin D levels and tuberculosis in 2008 had included 7 studies with 531 participants and reported that low serum vitamin D levels were associated with a higher risk of active TB. 10 However,there is paucity of relevant epidemiological data regarding vitamin D deficiency in paediatric tuberculosis.…”

Section: Discussionmentioning

confidence: 99%

A study of vitamin D status in children with tuberculosis in Peterborough, United Kingdom

Ahmed

Aslam

2015

Int J Contemp Pediatr

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INTRODUCTIONTuberculosis (TB) is an important public health problem in the United Kingdom and the recent data suggest that the incidence of TB in the UK remains high compared to most other Western European countries, with 8751 cases reported in 2012, an incidence of 13.9 per 100000 population. The majority of TB cases occurred in large urban centres, amongst young adults, those from countries with high TB burdens, and those with social risk factors for TB. 73% of TB cases were born outside the UK and the rate of TB among the non UK-born population is almost 20 times the rate in the UK-born. 1 The treatment of tuberculosis has been based on antituberculosis chemotherapy for the last few decades and there has been an ongoing research in newer treatment modalities. Vitamin D has been used in the treatment of TB in pre-antibiotic times. The emergence of TB sanatoriums in the 19 th century and popularity of heliotherapy and cod liver oil as treatments strategies indicate the possible role of vitamin D in management of ABSTRACT Background: We aimed to compare the prevalence of vitamin D deficiency and insufficiency in children with active or latent tuberculosis with the control population. Methods: This was a retrospective case control study and included 34 patients with evidence of exposure to tuberculosis and 34 controls reviewed at Peterborough city hospital from October 2011 to September 2013, who were matched with regards to age, gender and ethnicity. All patients had blood investigations, chest X-ray, Quantiferon Gold and Mantoux done at the time of review along with serum 25-hydroxyvitamin D concentrations in serum. Results: 73.6% of patients with Childhood Tuberculosis and 47.1 % of controls had low Vitamin D levels (deficiency and insufficiency). The median vitamin D level in children with tuberculosis was 34.75 nmol/l and in controls was 52.8 nmol/l. Patients older than 12 years of age had significantly lower serum 25-hydroxyvitamin D concentrations than those patients younger than 5 year of age. Gender, ethnicity, BMI, BCG status, serum calcium, serum phosphate and alkaline phosphatase had no significant correlation with vitamin D concentration in patients and controls. Conclusions:The present study demonstrated that children with evidence of exposure to Tuberculosis were more likely to be associated with lower levels of vitamin D than control population. Larger multi-centric randomized controlled trials are needed to prove the association between vitamin D and Tuberculosis. The association between low levels of vitamin D and tuberculosis suggests investigation for vitamin D deficiency in all children diagnosed with Tuberculosis and supplementation of these children with vitamin D.

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Section: Discussionmentioning

confidence: 99%

A study of vitamin D status in children with tuberculosis in Peterborough, United Kingdom

Ahmed

Aslam

2015

Int J Contemp Pediatr

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“…Several studies have linked vitamin D deficiency with an increased risk for susceptibility to active TB (Martineau et al ., 2007; Wejse et al ., 2007; Nnoaham and Clarke, 2008). The active form of vitamin D3 induces autophagy in primary human monocytes and THP‐1 macrophages via the expression of the anti‐microbial peptide cathelicidin, which activates transcription of the autophagy‐related genes encoding Beclin‐1 and ATG5 (Yuk et al ., 2009). In primary human macrophages and THP‐1 macrophages, active vitamin D3 also induces the localization of Mtb in autophagosomes in a cathelicidin‐dependent manner (Yuk et al ., 2009).…”

Section: Autophagy In the Immune Response To Tbmentioning

confidence: 99%

The innate immune response in human tuberculosis

2015

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Summary M ycobacterium tuberculosis (Mtb) infection can be cleared by the innate immune system before the initiation of an adaptive immune response. This innate protection requires a variety of robust cell autonomous responses from many different host immune cell types. However, Mtb has evolved strategies to circumvent some of these defences. In this mini‐review, we discuss these host–pathogen interactions with a focus on studies performed in human cells and/or supported by human genetics studies (such as genome‐wide association studies).

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“…For example, in HBV (hepatitis B virus)-infected hepatocytes, the HBV x protein increases autophagy by up-regulating the expression of Beclin 1 [160]. In human monocytes and human myeloid leukemia cells, vitamin D3 has been shown to induce autophagy by up-regulating both Beclin 1 and Atg5 [161,162]. The transcription factor implicated has not been identified, but it has been shown that in human monocytes the effect of Vitamin D3 is mediated via cathelicidin.…”

Section: Nf-κbmentioning

confidence: 99%

Overview of macroautophagy regulation in mammalian cells

et al. 2010

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Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGyrelated genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of autophagy is now better understood because of the discovery that the activity of Atg complexes is targeted by protein kinases, and owing to the importance of nuclear regulation via transcription factors in regulating the expression of autophagy genes.

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Vitamin D3 Induces Autophagy in Human Monocytes/Macrophages via Cathelicidin

Cited by 703 publications

References 45 publications

A study of vitamin D status in children with tuberculosis in Peterborough, United Kingdom

A study of vitamin D status in children with tuberculosis in Peterborough, United Kingdom

The innate immune response in human tuberculosis

Overview of macroautophagy regulation in mammalian cells

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