Rhinovirus-induces progression of lung disease in a mouse model of COPD via IL-33/ST2 signaling axis

Gimenes-Júnior, João Antonio; Srivastava, Vikram; Reddyvari, Hymavathi; Kotnala, Sudhir; Mishra, Rahul; Farazuddin, Mohammad; Li, Wuyan; Sajjan, Uma S.

doi:10.1042/cs20181088

Cited by 11 publications

(8 citation statements)

References 41 publications

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“…Macrophages are innate immune cells that play a critical role in resolving inflammation and defending against exogenous pathogens, contributing to lung homeostasis. 3 , 4 Macrophages are classified as classically activated (M1) or alternatively activated (M2). 5–7 M1 macrophages are induced by interferon-γ (IFN-γ) and lipopolysaccharide (LPS), produce inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α), and exert proinflammatory and cytotoxic effects.…”

Section: Introductionmentioning

confidence: 99%

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Liu¹,

Zhang²,

Yang³

et al. 2022

COPD

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Background Macrophage polarization plays an important role in the pathogenesis of COPD emphysema. Changes in macrophage polarization in COPD remain unclear, while polarization and ferroptosis are essential factors in its pathogenesis. Therefore, this study investigated the relationship between macrophage polarization and ferroptosis in COPD emphysema. Methods We measured macrophage polarization and the levels of matrix metalloproteinases (MMPs) in the lung tissues of COPD patients and cigarette smoke (CS)-exposed mice. Flow cytometry was used to determine macrophage (THP-M cell) polarization changes. Ferroptosis was examined by FerroOrange, Perls’ DAB, C11-BODIPY and 4-HNE staining. Nuclear receptor coactivator 4 (NCOA4) was measured in the lung tissues of COPD patients and CS-exposed mice by western blotting. A cell study was performed to confirm the regulatory effect of NCOA4 on macrophage polarization. Results Increased M2 macrophages and MMP9 and MMP12 levels were observed in COPD patients, CS-exposed mice and THP-M cells cocultured with CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased NCOA4 levels and ferroptosis were confirmed in COPD. Treatment with NCOA4 siRNA and the ferroptosis inhibitor ferrostatin-1 revealed an association between ferroptosis and M2 macrophages. These findings support a role for NCOA4, which induces an increase in M2 macrophages, in the pathogenesis of COPD emphysema. Conclusion In our study, CS led to the dominance of the M2 phenotype in COPD. We identified NCOA4 as a regulator of M2 macrophages and emphysema by mediating ferroptosis, which offers a new direction for research into COPD diagnostics and treatment.

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Section: Introductionmentioning

confidence: 99%

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Liu¹,

Zhang²,

Yang³

et al. 2022

COPD

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“…Macrophages are innate immune cells that play a key role in alleviating inflammation and defending against invasion by external pathogens (66,67). Studies found that macrophage activation is closely related to the occurrence of COPD, and the total number of macrophages is proportional to the severity of smoking and COPD (68).…”

Section: Role Of Ferroptosis In Copdmentioning

confidence: 99%

The molecular mechanism of ferroptosis and its role in COPD

et al. 2023

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Ferroptosis, a new type of cell death, is mainly characterized by intracellular iron accumulation and lipid peroxidation. The complex regulatory network of iron metabolism, lipid metabolism, amino acid metabolism, p53-related signaling, and Nrf2-related signaling factors is involved in the entire process of ferroptosis. It has been reported that ferroptosis is involved in the pathogenesis of neurological diseases, cancer, and ischemia–reperfusion injury. Recent studies found that ferroptosis is closely related to the pathogenesis of COPD, which, to some extent, indicates that ferroptosis is a potential therapeutic target for COPD. This article mainly discusses the related mechanisms of ferroptosis, including metabolic regulation and signaling pathway regulation, with special attention to its role in the pathogenesis of COPD, aiming to provide safe and effective therapeutic targets for chronic airway inflammatory diseases.

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“…Next, we examined whether DPP4 expression is associated with NTHi-induced lung inflammation in vivo by using mice displaying mild to moderate COPD-like lung disease (27,32,33). Our previous studies demonstrated that normal mice clear all the bacteria by 3 days postinfection and resolve bacteria-induced inflammation by day 7 (27,30).…”

Section: Nthi-infected Copd Mice Show Sustained Lung Inflammation and Increased Dpp4 Expressionmentioning

confidence: 99%

Contribution of dipeptidyl peptidase 4 to non-typeable Haemophilus influenzae-induced lung inflammation in COPD

et al. 2021

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Dipeptidyl peptidase 4 (DPP4) expression is increased in the lungs of chronic obstructive pulmonary disease (COPD). DPP4 is known to be associated with inflammation in various organs, including LPS-induced acute lung inflammation. Since non-typeable H. influenzae (NTHi) causes acute exacerbations in COPD patients, we examined the contribution of DPP4 in NTHi-induced lung inflammation in COPD. Pulmonary macrophages isolated from COPD patients showed higher expression of DPP4 than the macrophages isolated from normal subjects. In response to NTHi infection, COPD, but not normal macrophages show a further increase in the expression DPP4. COPD macrophages also showed higher expression of IL-1β, and CCL3 responses to NTHi than normal, and treatment with DPP4 inhibitor, diprotin A attenuated this response. To examine the contribution of DPP4 in NTHi-induced lung inflammation, COPD mice were infected with NTHi, treated with diprotin A or PBS intraperitoneally, and examined for DPP4 expression, lung inflammation and cytokine expression. Mice with COPD phenotype showed increased expression of DPP4, which increased further following NTHi infection. DPP4 expression was primarily observed in the infiltrated inflammatory cells. NTHi-infected COPD mice also showed sustained neutrophilic lung inflammation and expression of CCL3, and this was inhibited by DPP4 inhibitor. These observations indicate that enhanced expression of DPP4 in pulmonary macrophages may contribute to sustained lung inflammation in COPD following NTHi infection. Therefore, inhibition of DPP4 may reduce the severity of NTHi-induced lung inflammation in COPD.

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Rhinovirus-induces progression of lung disease in a mouse model of COPD via IL-33/ST2 signaling axis

Cited by 11 publications

References 41 publications

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

The molecular mechanism of ferroptosis and its role in COPD

Contribution of dipeptidyl peptidase 4 to non-typeable Haemophilus influenzae-induced lung inflammation in COPD

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