Challenges and Opportunities for Post-COVID Pulmonary Disease: A Focused Review of Immunomodulation

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3850 - 3850

Опубликована: Апрель 18, 2025

The resolution of the recent COVID-19 pandemic still requires attention, since consequences having suffered infection, even in mild cases, are associated with several acute and chronic pathological conditions referred to as post-COVID syndrome (PCS). PCS often manifests pulmonary disease and, up 9% a more serious complication known post-COVID-19 fibrosis (PC19-PF), which has similar clinical course idiopathic (IPF). Generating knowledge provide robust evidence about benefits different therapeutic strategies treat effects can new insights amplify options for these patients. We present found after scoping review, following extended PRIMSA guidelines, use immunomodulators PCS. start brief description immunomodulatory properties relevant drugs, their clinically proven efficacy viral infections inflammatory conditions, during pandemic. emphasize need well-designed trials improve our understanding physiopathology PC19-PF also determine safety candidate treatments.

Язык: Английский

Rutin ameliorates LPS-induced acute lung injury in mice by inhibiting the cGAS-STING-NLRP3 signaling pathway

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Май 8, 2025

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), represent critical failures with high mortality rates limited treatment options. While the flavonoid rutin exhibits documented anti-inflammatory antioxidant properties, therapeutic mechanisms in ALI/ARDS remain unclear. This study investigated rutin's efficacy against lipopolysaccharide (LPS)-induced ALI mice, a mechanistic focus on cGAS-STING pathway NLRP3 inflammasome activation. Male C57BL/6 mice were divided into Vehicle control, LPS induction, + co-treatment, Rutin monotherapy groups. was induced by intratracheal challenge, administered via gavage. Proteomics analysis, histological evaluation, immunohistochemistry, TUNEL staining, immunofluorescence, RT-qPCR, western blot, ELISA, oxidative stress assays performed to assess effects of ARDS. The proteomic profiling tissues from LPS-challenged identified significant dysregulation proteins integral cascade pyroptotic processes. Gene ontology KEGG analyses underscored pivotal role immune inflammatory responses ALI, particularly cytosolic DNA-sensing NOD-like receptor signaling pathways. administration significantly alleviated LPS-induced injury, reducing stress, apoptosis, proinflammatory cytokine levels (IL-6, IL-1β, TNF-α). Mechanistically, demonstrated dual suppression: 1) inhibiting activation through decreased expression cGAS, STING, phosphorylation TBK1/IRF3 (P<0.05), 2) attenuating NLRP3-mediated pyroptosis downregulation NLRP3-ASC-caspase1-GSDMD (P<0.05). Pharmacological STING inhibition (C-176) validated cGAS-STING-NLRP3 regulatory hierarchy pathogenesis. These findings elucidate novel mechanism coordinated suppression axis, positioning it as promising candidate for intervention.

Язык: Английский

CD163+ macrophages drive rapid pulmonary fibrosis via osteopontin secretion

International Immunopharmacology, Год журнала: 2025, Номер 161, С. 114976 - 114976

Опубликована: Июнь 3, 2025

Rapid pulmonary fibrosis (RPF) is a severe condition characterized by the rapid accumulation of excessive extracellular matrix (ECM), resulting in high mortality among patients with respiratory infections. CD163+ macrophages were found to be enriched RPF patients, their role this disease requires elucidation. We integrated single-cell RNA sequencing (scRNA-seq) and single-nucleus (snRNA-seq) analyses COVID-19-associated alongside an LPS three-hit-induced murine model vitro co-culture systems. Genetic (CD163-/- mice) functional (Osteopontin (OPN) silencing) approaches employed dissect profibrotic macrophages. scRNA-seq snRNA-seq identified enrichment lungs COVID-19 RPF, along upregulated expression fibrosis-associated genes, such as SPP1 (encoding OPN). In model, promoted progression, OPN positively correlating collagen deposition. Moreover, silencing impaired activity vitro. are mouse facilitating progression through secretion OPN. The macrophage-OPN axis could potential therapeutic target for fibrosis.

Язык: Английский