Vitamin�D reduces inflammatory response in asthmatic mice through HMGB1/TLR4/NF‑κB signaling pathway

Abstract

The present study aimed to investigate the effects of vitamin D (VD) on inflammatory responses in asthmatic mice and the underlying mechanism, providing a theoretical basis for clinical application of targeted drug therapy, and the development of novel drugs against asthma. Mouse models of asthma were established. Hematoxylin-eosin staining was performed to observe the pathological changes of the lung tissue. Pulmonary function tests were conducted to determine airway resistance in asthmatic mice. ELISA was performed to measure the serum levels of inflammatory factors. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were performed to determine the changes in apoptosis-inducing factors, and high mobility group box 1 protein (HMGB1)/Toll-like receptor-4 (TLR4)/nuclear factor (NF)-κB signaling pathway-related proteins. VD reduced infiltrated inflammatory factors, attenuated the airway resistance of asthmatic mice, decreased serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, increased serum levels of IL-10, decreased apoptotic factor Bcl-2-associated X and caspase-3 expression, downregulated HMGB1 and TLR4, NF-κB and phosphorylated-NF-κB p65 expression. When TLR4 expression was inhibited, the anti-inflammatory effects of VD were attenuated, and HMGB1, TLR4, NF-κB and p-NF-κB p65 expression was increased. VD was able reduce the inflammatory response of asthmatic mice and apoptosis in lung tissue through the HMGB1/TLR4/NF-κB signaling pathway.

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“…Thus, vitamin D raised serum levels of IL-10, reducing the inflammatory and apoptotic response in that asthmatic mouse model. 40 Of interest, vitamin D suppressed the synthesis of 8-isoprostane (8-iso), IL-6 and granulocyte colony-stimulating factor and macrophages in human bronchial epithelial cells exposed to contaminating particles. In addition, it increased expression of the antioxidant pathway gene G6PD and levels of oxidised glutathione, and therefore it is inferred that vitamin D appears to protect the lungs and airways in asthmatic pathology through its anti-inflammatory and antioxidant effects.…”

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