https://scholars.lib.ntu.edu.tw/handle/123456789/641285
標題: | Calcitriol attenuates poly(I:C)-induced lung injury in obese mice via modulating toll-like receptor 3- and renin-angiotensin system-associated signal pathways | 作者: | Yeh, Chiu-Li JIN-MING WU KUEN-YUAN CHEN MING-HSUN WU PO-JEN YANG PO-CHU LEE PO-DA CHEN Kuo, Ting-Chun Yeh, Sung-Ling MING-TSAN LIN |
關鍵字: | AT2R; Ang(1–7); IRF3; Interferon-β; MasR | 公開日期: | 15-二月-2024 | 卷: | 128 | 來源出版物: | International immunopharmacology | 摘要: | This study investigated the effects of calcitriol on polyinosinic-polycytidylic acid (poly(I:C))-induced acute lung injury (ALI) and its association with Toll-like receptor 3 (TLR3) and renin-angiotensin system (RAS) signal pathways in obese mice. Normal mice were fed a high-fat diet to induce obesity. Obese mice were divided into four groups: SS group, intratracheally instilled with saline and intravenous (IV) saline injection via tail vein; SD group, instilled with saline and IV calcitriol injection; PS group, instilled with poly(I:C) and IV saline injection; and PD group, instilled with poly(I:C) and IV calcitriol injection. All mice were sacrificed 12 or 24 h after poly(I:C) stimulation. The results showed that poly(I:C) instillation led to increased production of systemic inflammatory cytokines. In the lungs, the population of macrophages decreased, while more neutrophils were recruited. TLR3-associated genes including IRF3, nuclear factor-κB, interferon-β and phosphorylated IRF3 expression levels, were upregulated. The RAS-associated AT1R and ACE2 protein levels increased, whereas AT2R, Ang(1-7), and MasR levels decreased. Also, reduced tight junction (TJ) proteins and elevated lipid peroxide levels were observed 24 h after poly(I:C) stimulation. Compared to the PS group, the PD group exhibited reduced systemic and lung inflammatory cytokine levels, increased macrophage while decreased neutrophil percentages, downregulated TLR3-associated genes and phosphorylated IRF3, and polarized toward the RAS-AT2R/Ang(1-7)/MasR pathway in the lungs. Higher lung TJ levels and lower injury scores were also noted. These findings suggest that calcitriol treatment after poly(I:C) instillation alleviated ALI in obese mice possibly by downregulating TLR3 expression and tending toward the RAS-associated anti-inflammatory pathway. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/641285 | ISSN: | 15675769 | DOI: | 10.1016/j.intimp.2024.111522 |
顯示於: | 醫學系 |
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