YTHDF1-mediated m6A modification of GBP4 promotes M1 macrophage polarization in acute lung injury DOI Creative Commons

Fengan Cao,

Shilei Wang,

Qiuyue Tan

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 13, 2025

Acute lung injury (ALI) is a severe condition with multifaceted causes, including inflammation and oxidative stress. This research investigates the influence of m6A (N6-methyladenosine) modification on GBP4, protein pivotal for macrophage polarization, critical immune response in ALI. Utilizing mouse model to induce ALI, study analyzed GBP4 expression alveolar macrophages. By overexpressing or knocking down assessed its impact M1 polarization. The role YTHDF1 was also explored through knockdown experiments determine effect Increased noted ALI mice, promoting found enhance by recognizing sites mRNA, which linked reduced MLE-12 cells upon knockdown. emphasizes crucial roles development regulation. It suggests as potential therapeutic target, contributing understanding ALI's molecular mechanisms guiding future treatment strategies.

Language: Английский

Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients DOI Creative Commons

Audrey Cambon,

Christophe Guervilly, Clémence Delteil

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

COVID-19-associated acute-respiratory distress syndrome (C-ARDS) results from a direct viral injury associated with host excessive innate immune response mainly affecting the lungs. However, cytokine profile in lung compartment of C-ARDS patients has not been widely studied, nor compared to non-COVID related ARDS (NC-ARDS). To evaluate caspase-1 activation, IL-1 signature, and other inflammatory pathways tissue damage using post-mortem tissues, bronchoalveolar lavage fluids (BALF), serum across spectrum COVID-19 severity. Histological features were described activated-caspase-1 labeling was performed 40 biopsies. Inflammatory cytokines quantified BALF 19 steroid-treated-C-ARDSand NC-ARDS. Cytokine concentrations also measured 128 at different severity stages. Typical "diffuse alveolar damage" biopsies activated expression vascular lesions. Soluble Caspase-1p20, IL-1β, IL-1Ra, IL-6 lower level IFNγ CXCL-10, highly elevated steroid-treated-C-ARDS as well IL-1β appeared concentrated BALF, whereas circulating IL-1Ra comparable those correlated TNFα, TNFR1 CXCL8 however, significantly higher NC-ARDS C-ARDS, treated by steroid. In lungs both activation predominant IL-1β/IL-6 signature -associated chemokines are despite steroid treatment. These may be specifically targeted improve treatment limit damage.

Language: Английский

Citations

1
Chaihuang Qingfu Pills Protect Against Acute Pancreatitis—Associated Acute Lung Injury Through MMP9-NLRP3-Pyroptosis Pathway DOI Creative Commons
Wen Xiao, Huiying Shi, Yuan Tian

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2317 - 2338

Published: Feb. 1, 2025

Severe acute pancreatitis associated with lung injury (SAP-ALI) is a critical condition high mortality rate. Investigating the pathogenesis of SAP-ALI and developing effective treatments are urgently needed. Chaihuang Qingfu Pills (CHQF), traditional Chinese medicine modified from Qingyi Decoction, has been approved for treating (AP). However, its role in underlying mechanisms remain unclear. 92 AP patients were enrolled to observe protective effect CHQF on AP-ALI. L-arginine was used establish animal model. UHPLC-MS/MS identify components absorbed into serum. Transcriptomics analysis, network pharmacology, proteomics approaches explore molecular mechanism. In vivo vitro experiments conducted validate relevant findings. Clinical data indicated reduced incidence ALI 58.33% 36.36% patients. Animal demonstrated that decreased mortality, attenuated organ damage, inhibited systemic inflammation pathological SAP mice. Differential expression analysis weighted gene co-expression (WGCNA) identified 146 SAP-related differentially expressed genes (DEGs) GSE194331 dataset. acquired 26 blood 271 therapeutic targets. Integrated obtained 52 core targets SAP. Proteomic 216 proteins treatment SAP-ALI. Joint found MMP9 NLRP3 only common Both confirmed levels pyroptosis alveolar macrophages (AMs) under conditions. Moreover, inhibitor suppressed AMs pyroptosis. exerted by inhibiting macrophage through MMP9-NLRP3 pathway, providing novel strategy

Language: Английский

Citations

1
NLRP3 Inflammasome-mediated pyroptosis in acute lung injury: Roles of main lung cell types and therapeutic perspectives DOI
Jing Wang, Lulu Li, Zhen‐Ao Zhao

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114560 - 114560

Published: April 7, 2025

Language: Английский

Citations

0
YTHDF1-mediated m6A modification of GBP4 promotes M1 macrophage polarization in acute lung injury DOI Creative Commons

Fengan Cao,

Shilei Wang,

Qiuyue Tan

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 13, 2025

Acute lung injury (ALI) is a severe condition with multifaceted causes, including inflammation and oxidative stress. This research investigates the influence of m6A (N6-methyladenosine) modification on GBP4, protein pivotal for macrophage polarization, critical immune response in ALI. Utilizing mouse model to induce ALI, study analyzed GBP4 expression alveolar macrophages. By overexpressing or knocking down assessed its impact M1 polarization. The role YTHDF1 was also explored through knockdown experiments determine effect Increased noted ALI mice, promoting found enhance by recognizing sites mRNA, which linked reduced MLE-12 cells upon knockdown. emphasizes crucial roles development regulation. It suggests as potential therapeutic target, contributing understanding ALI's molecular mechanisms guiding future treatment strategies.

Language: Английский

Citations

0