PMID- 35915936 OWN - NLM STAT- MEDLINE DCOM- 20220803 LR - 20220803 IS - 1001-9391 (Print) IS - 1001-9391 (Linking) VI - 40 IP - 7 DP - 2022 Jul 20 TI - [The role of STAT-6/KLF-4/PPAR-gamma activation in alveolar macrophage polarization changes in silica-induced pulmonary fibrosis]. PG - 481-486 LID - 10.3760/cma.j.cn121094-20211101-00532 [doi] AB - 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) /Kruppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-gamma (PPAR-gamma) 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 mul crystalline SiO(2) suspension (20 mg/ml) or 100 mul 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) -1beta, tumor necrosis factor-alpha (TNF-alpha) , IL-6, IL-10, transforming growth factor-beta (TGF-beta) , STAT-6, KLF-4 and PPAR-gamma were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1beta, TNF-alpha, IL-6, IL-10 and TGF-beta 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-gamma 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-beta in crystalline SiO(2) group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1beta, TNF-alpha, IL-6 in crystalline SiO(2) group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-gamma and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-gamma 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-gamma signaling pathway. FAU - Yao, Z M AU - Yao ZM AD - Department of Occupation Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, China. FAU - Zhang, X AU - Zhang X AD - Department of Occupation Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, China. FAU - Yang, S X AU - Yang SX AD - Department of Special Medicine, School of Basic Medicine, Anhui Medical University, Hefei 230032, China. FAU - Zhu, J J AU - Zhu JJ AD - Department of Occupation Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, China. FAU - Hu, X X AU - Hu XX AD - Department of Occupation Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, China. FAU - Shen, T AU - Shen T AD - Department of Occupation Health and Environment Health, School of Public Health, Anhui Medical University, Hefei 230032, China. LA - chi GR - 81773467/The National Natural Science Foundation of China/ GR - J2019Y06/Hefei Independent Innovation Policy "Borrowing to Subsidize" Project/ PT - Journal Article PL - China TA - Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi JT - Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases JID - 8410840 RN - 0 (Interleukin-6) RN - 0 (Kruppel-Like Factor 4) RN - 0 (PPAR gamma) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 7631-86-9 (Silicon Dioxide) SB - IM MH - Animals MH - Interleukin-10/adverse effects/metabolism MH - Interleukin-6/metabolism MH - Kruppel-Like Factor 4 MH - *Macrophages, Alveolar/metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - PPAR gamma/metabolism/pharmacology MH - *Pulmonary Fibrosis/metabolism MH - RNA, Messenger/metabolism MH - Silicon Dioxide/toxicity MH - Transforming Growth Factor beta/genetics MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Alveolar macrophages OT - Polarization OT - Pulmonary fibrosis OT - Silicon dioxide EDAT- 2022/08/03 06:00 MHDA- 2022/08/04 06:00 CRDT- 2022/08/02 02:48 PHST- 2022/08/02 02:48 [entrez] PHST- 2022/08/03 06:00 [pubmed] PHST- 2022/08/04 06:00 [medline] AID - 10.3760/cma.j.cn121094-20211101-00532 [doi] PST - ppublish SO - Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022 Jul 20;40(7):481-486. doi: 10.3760/cma.j.cn121094-20211101-00532.