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How silicosis is fought by Vitamin D (in mice) - several studies

Vitamin D protects silica particles induced lung injury by promoting macrophage polarization in a KLF4-STAT6 manner - Dec 2022

J of Nutritional Biochemistry, Volume 110, December 2022, 109148
PDF is behind a $28 paywall https://doi.org/10.1016/j.jnutbio.2022.109148s
Youjing Yang ab1 Shuhui Weib 1 QianminLibKaimiaoChubYujiaZhoubLianXuebHailinTianbShashaTaoab

Silicosis is one of the severest occupational diseases worldwide, manifesting as infiltration of inflammatory cells, excessive secretion of pro-inflammatory mediators and pulmonary diffuse fibrosis. Macrophages polarization to M2 is one of the major strategies that attenuates inflammatory response.
Our previous study found that vitamin D could protect against silica-induced lung injury by damping the secretion of pro-inflammatory cytokines. Here we further identified that vitamin D attenuated silica particles-induced lung inflammation by regulating macrophage polarization in a KLF4-STAT6 manner. Myeloid-specific Stat6 knockout (cKO) mice were generated for in vivo studies. Primary macrophages purified from bronchoalveolar lavage fluid (BALF) of wildtype or Stat6 cKO mice and differentiated THP-1 cells were used for in vitro studies. Vitamin D was found to promote alveolar macrophage polarizing to M2 phenotype through the STAT6 signaling pathway, as demonstrated by worse lung inflammation and ablated protection of vitamin D in silica particles-instilled Stat6 cKO mice.
Mechanismly, vitamin D upregulated KLF4 expression in the alveolar macrophage, which synergistically activated STAT6. Additionally, KLF4 was found to upregulate macrophages autophagy, which protected them from silica particles-induced oxidative stress and cell apoptosis. The protective effects of vitamin D were dismissed by silencing KLF4. Our study demonstrates the potential mechanism of vitamin D-mediated macrophage polarization and reveals the therapeutic application of vitamin D in inflammatory disease.

Vitamin D ameliorates silica particles-induced pulmonary injury by inhibiting related inflammatory cytokines and promoting macrophage polarizing to anti-inflammatory M2 phenotype based on STAT6 signaling pathway. Mechanismly, vitamin D induces the expression of KLF4, which synergistically activates STAT6 and promotes its nucleus translocation and then transcripts downstream genes, which promote macrophages polarizing to M2. In addition, vitamin D also up-regulates autophagy in macrophages against cell apoptosis through KLF4.

Prevous publication by the authors: Silicosis reduces vitamin D levels – Jan 2016

Mice getting very high-dose Vitamin D did not get silicosis - Dec 2021

Upregulation of autophagy in M2 macrophage by vitamin D alleviates crystalline silica-induced pulmonary inflammatory damage - Dec 2021
Ecotoxicology and Environmental Safety. Vol 225, 1 Dec 2021, 112730, https://doi.org/10.1016/j.ecoenv.2021.112730
Youjing Yanga ShuhuiWeia Kaimiao Chua QianminLiaYujiaZhouaYuMabLianXueaHailinTianaShashaTaoab

Crystalline silica (CS) is a universal environmental pollutant, which causes a typical inflammatory lung injury. Vitamin D shows huge potential against particles-induced lung injury, while little known about the molecular mechanism involved in macrophage autophagy. In this study, we aim to identify the protective effects of vitamin D on CS caused lung inflammatory injury and clarify the detail mechanism. After exposure to CS (3 mg/mice in 50 μl PBS), wildtype and Atg7flox/flox Lyz2-cre mice were treated with or without vitamin D3 (40,000 IU/kg). The results indicated that exposure to CS caused an obvious lung injury, manifesting as pathological structural changes, macrophage-dominated inflammatory cell infiltration and increased pro-inflammatory cytokines. Remarkably, these damages were more serious in Atg7flox/flox Lyz2-cre mice.
Vitamin D was found to inverse CS-induced inflammatory cell infiltration and restored anti-inflammatory M2 macrophages by inducing autophagy, which attenuated lung injury, as determined by decreased levels of apoptosis and inflammatory response. While, this effects of vitamin D were slashed in Atg7flox/flox Lyz2-cre mice. This study reveals the adverse effect of CS on lung tissue and the protective mechanism of vitamin D involved in M2 macrophages autophagy, which attenuates CS-caused lung injury.
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VitaminDWiki - 8 studies in both categories Breathing and Inflammation

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