The role of STAT-6/KLF-4/PPAR-γ activation in alveolar macrophage polarization changes in silica-induced pulmonary fibrosis
10.3760/cma.j.cn121094-20211101-00532
- VernacularTitle:STAT-6/KLF-4/PPAR-γ激活在二氧化硅致肺纤维化中肺泡巨噬细胞极化改变中的作用
- Author:
Zhuomeng YAO
1
;
Xiang ZHANG
;
Shuxin YANG
;
Jiaojiao ZHU
;
Xinxin HU
;
Tong SHEN
Author Information
1. 安徽医科大学公共卫生学院职业卫生与环境卫生学系，合肥 230032
- Keywords:
Pulmonary fibrosis;
Silicon dioxide;
Alveolar macrophages;
Polarization
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2022;40(7):481-486
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of silicon dioxide (SiO 2) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods:In November 2020, C57BL/6 mice were randomly divided into crystalline SiO 2 group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 μl crystalline SiO 2 suspension (20 mg/ml) or 100 μl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1β, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-β (TGF-β) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1β, TNF-α, IL-6, IL-10 and TGF-β were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results:After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO 2 group. Compared with NS group, HYP level of lung tissue in crystalline SiO 2 group were increased, the proportion of M2-typed AMs in crystalline SiO 2 group was increased, the proportion of M1-typed AMs in crystalline SiO 2 group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-β in crystalline SiO 2 group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1β, TNF-α, IL-6 in crystalline SiO 2 group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO 2 group, and the the differences were statistically significant ( P<0.05) . Conclusion:Crystalline SiO 2 may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.
