HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responses

Abstract HSF1, SIRPα, and Dectin-1 play crucial roles in immune regulation and inflammatory responses, their rols in asthma remained unclear, thereby the study was carried on. Twenty-one SPF-grade C57BL/6 mice were randomly divided into three groups: sham group, Model group, and Model + HSF1A group,...

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Main Authors: Xiaojuan Liu, Yingqian Zhang, Huifang Wu, Jingli Zhang, Yingxue Wang, Huifeng Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-13531-0
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author Xiaojuan Liu
Yingqian Zhang
Huifang Wu
Jingli Zhang
Yingxue Wang
Huifeng Zhang
author_facet Xiaojuan Liu
Yingqian Zhang
Huifang Wu
Jingli Zhang
Yingxue Wang
Huifeng Zhang
author_sort Xiaojuan Liu
collection DOAJ
description Abstract HSF1, SIRPα, and Dectin-1 play crucial roles in immune regulation and inflammatory responses, their rols in asthma remained unclear, thereby the study was carried on. Twenty-one SPF-grade C57BL/6 mice were randomly divided into three groups: sham group, Model group, and Model + HSF1A group, with seven mice in each group. Except for the sham group, the other two groups were induced with OVA to establish an asthma model. The Model + HSF1A group was additionally treated with HSF1A. General conditions of the mice were observed. Lung tissue damage was assessed with Masson staining. RAW264.7 cells were divided into NC group, OVA + LPS group, HSF1A + OVA + LPS group, KRIBB11 + OVA + LPS group, SIRPα-OE + KRIBB11 + OVA + LPS group, SIRPα-OE + OVA + LPS group and SIRPα-KD + KRIBB11 + OVA + LPS group. The levels of GSH, MDA, IL-1β and TNFα in serum and cell supernatants were determined by ELISA. Protein expression in lung tissue and RAW264.7 cells was detected by Western blotting. In in vivo experiments, OVA-induced asthmatic mice exhibited severe airway resistance, collagen deposition, and elevated ROS and pro-inflammatory cytokines.HSF1A treatment improved lung function, reduced fibrosis, and restored redox balance. In vitro, HSF1A enhanced SIRPα expression and inhibited SYK/Dectin-1 signaling in LPS/OVA-stimulated macrophages, whereas HSF1 knockdown exacerbated inflammation. overexpression of SIRPα reversed KRIBB11-induced SYK activation, confirming the regulatory role of HSF1. HSF1 in macrophages regulates ROS and inflammatory responses by modulating the SIRPα/Dectin-1/SYK balance, thereby inhibiting the progression of asthma.
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spelling doaj-art-a5fa25e6bd5249dc8166630f615571c82025-08-20T03:05:21ZengNature PortfolioScientific Reports2045-23222025-08-0115111210.1038/s41598-025-13531-0HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responsesXiaojuan Liu0Yingqian Zhang1Huifang Wu2Jingli Zhang3Yingxue Wang4Huifeng Zhang5Department of Hebei Medical UniversityHebei Children’s Hospital Third Department of RespirationHebei Children’s Hospital Third Department of RespirationHebei Children’s Hospital Third Department of RespirationHebei Children’s Hospital Third Department of RespirationThe Department of Pediatrics, The Second Hospital of Hebei Medical UniversityAbstract HSF1, SIRPα, and Dectin-1 play crucial roles in immune regulation and inflammatory responses, their rols in asthma remained unclear, thereby the study was carried on. Twenty-one SPF-grade C57BL/6 mice were randomly divided into three groups: sham group, Model group, and Model + HSF1A group, with seven mice in each group. Except for the sham group, the other two groups were induced with OVA to establish an asthma model. The Model + HSF1A group was additionally treated with HSF1A. General conditions of the mice were observed. Lung tissue damage was assessed with Masson staining. RAW264.7 cells were divided into NC group, OVA + LPS group, HSF1A + OVA + LPS group, KRIBB11 + OVA + LPS group, SIRPα-OE + KRIBB11 + OVA + LPS group, SIRPα-OE + OVA + LPS group and SIRPα-KD + KRIBB11 + OVA + LPS group. The levels of GSH, MDA, IL-1β and TNFα in serum and cell supernatants were determined by ELISA. Protein expression in lung tissue and RAW264.7 cells was detected by Western blotting. In in vivo experiments, OVA-induced asthmatic mice exhibited severe airway resistance, collagen deposition, and elevated ROS and pro-inflammatory cytokines.HSF1A treatment improved lung function, reduced fibrosis, and restored redox balance. In vitro, HSF1A enhanced SIRPα expression and inhibited SYK/Dectin-1 signaling in LPS/OVA-stimulated macrophages, whereas HSF1 knockdown exacerbated inflammation. overexpression of SIRPα reversed KRIBB11-induced SYK activation, confirming the regulatory role of HSF1. HSF1 in macrophages regulates ROS and inflammatory responses by modulating the SIRPα/Dectin-1/SYK balance, thereby inhibiting the progression of asthma.https://doi.org/10.1038/s41598-025-13531-0AsthmaHSF1InflammationROSSIRPα/Dectin-1/SYK
spellingShingle Xiaojuan Liu
Yingqian Zhang
Huifang Wu
Jingli Zhang
Yingxue Wang
Huifeng Zhang
HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responses
Scientific Reports
Asthma
HSF1
Inflammation
ROS
SIRPα/Dectin-1/SYK
title HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responses
title_full HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responses
title_fullStr HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responses
title_full_unstemmed HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responses
title_short HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/ SYK mediated ROS and inflammatory responses
title_sort hsf1 in macrophages suppressed the progression of asthma via modulating sirpα shp2 dectin 1 syk mediated ros and inflammatory responses
topic Asthma
HSF1
Inflammation
ROS
SIRPα/Dectin-1/SYK
url https://doi.org/10.1038/s41598-025-13531-0
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