Crosstalk between ROS-inflammatory gene expression axis in the progression of lung disorders

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Язык: Английский

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Macrophage Implication in IPF: Updates on Immune, Epigenetic, and Metabolic Pathways

Cells, Год журнала: 2023, Номер 12(17), С. 2193 - 2193

Опубликована: Сен. 1, 2023

Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease of unknown etiology with poor prognosis. It chronic and progressive that has distinct radiological pathological pattern from common pneumonia. The use immunosuppressive medication was shown to be completely ineffective in clinical trials, resulting years neglect the immune component. However, recent developments fundamental translational science demonstrate cells play significant regulatory role IPF, macrophages appear among most crucial. These highly plastic generate multiple growth factors mediators affect initiation progression IPF. In this review, we will provide an update on IPF through systemic discussion various mechanisms involving receptors, cytokines, metabolism, epigenetics.

Язык: Английский

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Favipiravir ameliorates bleomycin-induced pulmonary fibrosis by reprogramming M1/M2 macrophage polarization

International Immunopharmacology, Год журнала: 2024, Номер 131, С. 111774 - 111774

Опубликована: Март 14, 2024

Язык: Английский

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The IL-4/13-induced production of M2 chemokines by human lung macrophages is enhanced by adenosine and PGE2

International Immunopharmacology, Год журнала: 2024, Номер 128, С. 111557 - 111557

Опубликована: Янв. 23, 2024

Lung macrophages (LMs) are critically involved in respiratory diseases. The primary objective of the present study was to determine whether or not an adenosine analog (NECA) and prostaglandin E2 (PGE2) affected interleukin (IL)-4- IL-13-induced release M2a chemokines (CCL13, CCL17, CCL18, CCL22) by human LMs. Primary isolated from resected lungs were incubated with NECA, PGE2, roflumilast, vehicle stimulated IL-4 IL-13 for 24 h. levels PGE2 culture supernatants measured using ELISAs enzyme immunoassays. Exposure (10 ng/mL) (50 associated greater chemokine production but production. NECA (10-6 M) induced a lesser extent significantly enhanced IL-4/IL-13-induced these chemokines. At either clinically relevant concentration (10-9 at (10-7 that fully inhibited phosphodiesterase 4 (PDE4) activity, roflumilast did increase modulate their production, regardless presence absence PGE2. inhibition PDE4 alter These results contrast totally previously reported inhibitory effects inhibitors on lipopolysaccharide-induced tumor necrosis factor alpha M1

Язык: Английский

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Autologous precision-cut lung slice co-culture models for studying macrophage-driven fibrosis

Frontiers in Physiology, Год журнала: 2025, Номер 16

Опубликована: Янв. 31, 2025

Precision-cut lung slices (PCLS) are commonly used as an ex vivo model to study fibrosis; however, traditional models lack immune cell infiltration, including the recruitment of monocytes and macrophages, which critical for inflammation fibrosis. To address this limitation, we developed novel autologous PCLS-immune co-culture that better replicate processes inflammation, repair, associated with Fibrotic responses nicotine, cigarette smoke extract (CSE), a fibrosis-inducing cocktail (FC) were first evaluated in PCLS containing only tissue-resident upregulation α-SMA-expressing fibroblasts confirmed by immunofluorescence Western blotting, collagen deposition quantified using Sirius Red staining. macrophage recruitment, employed indirect transwells approximate blood vessel function. Chemotactic studies revealed increased migration bone marrow-derived macrophages (BMDMs) toward infiltration into CSE-injured PCLS. In direct simulating repair phase fibrosis, exposed CSE FC showed further presence BMDMs, but not heterologous ones. These findings suggest our provide platform studying involvement fibrosis offer potential developing macrophage-targeted therapeutic strategies pulmonary

Язык: Английский

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Reducing M2 macrophage in lung fibrosis by controlling anti-M1 agent

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 3, 2025

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by excessive scarring and due to the abnormal accumulation of extracellular matrix components, primarily collagen. This study aims design solve an optimal control problem regulate M2 macrophage activity in IPF, thereby preventing formation controlling anti-M1 agent. The research models diffusion macrophages inflamed tissue using novel dynamical system with partial differential equation (PDE) constraints. formulated minimize regulating employs two-step process discretization followed optimization, utilizing Galerkin spectral method transform PDE into algebraic ordinary equations (ODEs). then solved Pontryagin/s minimum principle, canonical Hamiltonian equations, extended Riccati equations. numerical simulations indicate that without control, levels increase stabilize, contributing fibrosis. In contrast, strategy effectively reduces macrophages, within 120 days. results highlight potential proposed approach modulating repair processes mitigating progression IPF. underscores significance targeting employing mathematical methods develop innovative therapies for

Язык: Английский

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CC-chemokine ligand 18, CXC motif chemokine 13 and osteopontin as biomarkers of silicosis and asbestosis: a prospective observational study

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 25, 2025

Silicosis and asbestosis, distinct forms of pneumoconiosis, manifest progressive interstitial fibrosis due to exposure silica dust or asbestos fibers. This study aimed identify potential biomarkers for diagnosing silicosis while also evaluating disease severity prognosis. We undertook an prospective observational involving patients with asbestosis. The correlation between baseline CC-chemokine ligand 18 (CCL18), CXC motif chemokine 13 (CXCL13), osteopontin (OPN), periostin, fibulin-3 clinical variables was analyzed. Diagnostic sensitivity evaluated using receiver operating characteristic curves, correlations biomarker levels were Multivariable Cox regression assessed the concentrations' strength in predicting all-cause mortality Of 231 163 asbestosis included study, 29 (12.6%) 28 (17.2%) died within five years follow-up period. Elevated concentrations CCL18, CXCL13, OPN observed compared 118 HCs. accuracy order, OPN, CXCL13. Combining CXCL13 enhanced diagnostic accuracy. In patients, these significantly associated lung function values. However, not risk factor mortality. stand out as promising Meanwhile, may be used evaluation conditions.

Язык: Английский

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Caveolin Scaffolding Domain (CSD) Peptide LTI-2355 Modulates the Phagocytic and Synthetic Activity of Lung-Derived Myeloid Cells in Idiopathic Pulmonary Fibrosis (IPF) and Post-Acute Sequelae of COVID Fibrosis (PASC-F)

Biomedicines, Год журнала: 2025, Номер 13(4), С. 796 - 796

Опубликована: Март 26, 2025

Rationale: The role of the innate immune system in idiopathic pulmonary fibrosis (IPF) remains poorly understood. However, a functional myeloid compartment is required to remove dying cells and cellular debris, as well mediate responses against pathogens. Aberrant macrophage activity has been described patients with post-acute sequelae COVID (PASC-F), caveolin scaffolding domain (CSD) peptides have found attenuate inflammation mouse lung injury models. Therefore, we examined, for first time, effects CSD peptide LTI-2355 on synthetic properties human isolated from explant tissue donor lungs IPF PASC-F tissue. Methods Results: CD45+ exhibited an impaired capacity clear autologous dead debris. uptake pathogen-coated bioparticles was both fibrotic patient groups independent type pathogen, highlighting intrinsic cell impairment. improved phagocytic cells, this improvement paired decreased proinflammatory pro-fibrotic activity. also shown primarily target CD206-expressing cells. Conclusions: Primary exhibit dysfunctional that are modulated by LTI-2355. treatment resulted significantly reduced sCD163, IFN-α2, IFN-γ, IL-2, IL-10, IL-12p40, MMP-1 supernatant. This study highlights additional mechanism action progressive disease.

Язык: Английский

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Discovery of sinomenine derivatives inhibiting macrophage polarization against rheumatoid arthritis through selectively targeting heme oxygenase-1

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 117596 - 117596

Опубликована: Апрель 1, 2025

Язык: Английский

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Calcaratarin D, A Labdane Diterpenoid, Attenuates Bleomycin-Induced Pulmonary Fibrosis by Blocking Wnt/β-Catenin Signaling Pathway

Pharmacological Research, Год журнала: 2025, Номер 216, С. 107756 - 107756

Опубликована: Апрель 29, 2025

Idiopathic pulmonary fibrosis (IPF) is one of the most common interstitial lung diseases with a high mortality rate. Calcaratarin D (CalD), labdane diterpenoid, has been shown to possess anti-inflammatory properties. The present study evaluated therapeutic potential CalD in fibrosis. A single dose bleomycin (BLM, 2.5mg/kg) was instilled intratracheally mice for up 21 days develop Oral (50mg/kg) reduced BLM-induced inflammatory cell infiltration, especially pro-fibrotic Arg1-expressing macrophages bronchoalveolar lavage fluid. During late fibrotic phase, decreased and body weight loss. In addition, ameliorated histopathology, collagen deposition mucus hypersecretion, improved functions BLM-exposed mice. Furthermore, modulated levels pro-inflammatory cytokines, chemokines, growth factors BAL fluid tissues. mouse lungs, BLM selectively upregulated Wnt10A level promoted β-catenin nuclear translocation. not only blocked Wnt10A/β-catenin signaling pathway but also markers such as collagens, α-SMA FHL2. normal human fibroblasts, inhibited TGF-β1-stimulated Wnt/β-catenin by reducing production, upregulating endogenous Wnt antagonist DKK1 level, dephosphorylating ligand co-receptor LRP6, preventing YAP/TAZ antifibrotic action be dependent on its α,β-unsaturated γ-butyrolactone structure that essential form covalent interaction cellular protein targets. Our results imply could novel agent IPF, acting through blockade pathway.

Язык: Английский

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