Role of metalloproteinases and TNF-α in obesity-associated asthma in mice

Vieira, Cristiano Pedrozo; Oliveira, Letícia Prado; Silva, Mariana Bombardi Da; André, Diana Majolli; Tavares, Edith Bastos Gandra; Pimentel, Edson Rosa; Antunes, Edson

doi:10.1016/j.lfs.2020.118191

Cited by 15 publications

(7 citation statements)

References 46 publications

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“…Kaempferol can inhibit ceramide signaling pathway, which reduce the release of TNF- α , reduce the transcription of MMP genes, and reduce the expression of MMP. Due to the reduced expression of MMP, it can effectively protect the extracellular membrane (ECM) and basement membrane in the lung from dissolution and avoid asthma symptoms [ 15 ]. Paeoniflorin attenuates adipocyte lipolysis and inhibits the phosphorylation of ERK, JNK, and IKK stimulated by TNF- α [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Analysis of the Identification of Phytochemicals and Therapeutic Mechanisms of Paeoniae Radix Alba for the Treatment of Asthma

Wang

Peng

Jin

et al. 2021

Journal of Immunology Research

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Background. Paeoniae Radix Alba (PRA), the root of the plant Paeonia lactiflora Pall., has been suggested to play an important role for the treatment of asthma. A biochemical understanding of the clinical effects of Paeoniae Radix Alba is needed. Here, we explore the phytochemicals and therapeutic mechanisms via a systematic and comprehensive network pharmacology analysis. Methods. Through TCMSP, PubChem, GeneCards database, and SwissTargetPrediction online tools, potential targets of active ingredients from PRA for the treatment of asthma were obtained. Cytoscape 3.7.2 was used to determine the target of active ingredients of PRA. Target protein interaction (PPI) network was constructed through the STRING database. The Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genes (KEGG) pathway enrichment analysis were analyzed through the biological information annotation database (DAVID). Results. Our results indicate that PRA contains 21 candidate active ingredients with the potential to treat asthma. The enrichment analysis of GO and KEGG pathways found that the treatment of asthma by PRA may be related to the process of TNF (tumor necrosis factor) release, which can regulate and inhibit multiple signaling pathways such as ceramide signaling. Conclusions. Our work provides a phytochemical basis and therapeutic mechanisms of PRA for the treatment of asthma, which provides new insights on further research on PRA.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology Analysis of the Identification of Phytochemicals and Therapeutic Mechanisms of Paeoniae Radix Alba for the Treatment of Asthma

Wang

Peng

Jin

et al. 2021

Journal of Immunology Research

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“…Increased circulating adipokines, as well as elevated levels of IL-1β and TNF-α are associated with asthma in obese individuals, but not with allergic asthma [ 9 , 46 ]. Moreover, IL-1β and TNF-α have been indicated to play a prominent role in the development of AHR and neutrophilic airway inflammation [ 47 , 48 ]. TNF-α blockade or depletion of alveolar macrophages in the obese mice could decrease AHR [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice

Lin

Wang

et al. 2023

Respir Res

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Obesity increases the severity of airway hyperresponsiveness (AHR) in individuals with asthma, but the mechanism is not well elucidated. G-protein coupled receptor 40 (GPR40) has been found to induce airway smooth muscle contraction after activated by long-chain fatty acids (LC-FFAs), suggesting a close correlation between GPR40 and AHR in obese. In this study, C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity with or without ovalbumin (OVA) sensitization, the regulatory effects of GPR40 on AHR, inflammatory cells infiltration, and the expression of Th1/Th2 cytokines were evaluated by using a small-molecule antagonist of GPR40, DC260126. We found that the free fatty acids (FFAs) level and GPR40 expression were greatly elevated in the pulmonary tissues of obese asthmatic mice. DC260126 greatly reduced methacholine-induced AHR, ameliorated pulmonary pathological changes and decreased inflammatory cell infiltration in the airways in obese asthma. In addition, DC260126 could down-regulate the levels of Th2 cytokines (IL-4, IL-5, and IL-13) and pro-inflammatory cytokines (IL-1β, TNF-α), but elevated Th1 cytokine (IFN-γ) expression. In vitro, DC260126 could remarkedly reduce oleic acid (OA)-induced cell proliferation and migration in HASM cells. Mechanistically, the effects that DC260126 alleviated obese asthma was correlated with the down-regulation of GTP-RhoA and Rho-associated coiled-coil-forming protein kinase 1 (ROCK1). Herein, we proved that targeting of GPR40 with its antagonist helped to mitigate multiple parameters of obese asthma effectively.

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“…IL-4, IL-5 and TNF-α play an important role in the infiltration of eosinophils into vascular cell adhesion molecule-1 (VCAM-1) and causes the transendothelial migration of eosinophils ( Steinke and Borish, 2001 ), while IL-5 strongly promotes the maturation adhesion and activation of eosinophils ( Matucci et al, 2019 ). Inhibition of TNF-α can significantly reduce the imbalance of metalloproteinases in asthma ( Vieira et al, 2020 ). We chose to detect IL-4, IL-5, and TNF-α by using Luminex liquid suspension chip.…”

Section: Discussionmentioning

confidence: 99%

Allergic Asthma-Induced Cognitive Impairment is Alleviated by Dexamethasone

et al. 2021

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Allergic asthma is a typical chronic inflammatory disease of respiratory tract. Clinical data shows that patients with allergic asthma have different degrees of cognitive dysfunction. The molecular mechanism underlying the pathogenesis of asthma-induced cognitive disorder is not yet well defined. Dexamethasone (DEX), one of the first-line drugs being widely used in the treatment of asthma, has not been reported to have an effect on cognitive dysfunction in mice model. To investigate the effect of asthma on cognitive impairment as well as the effect of DEX on asthma-caused morphological and behavioral changes, C57BL/6J mice received treatment with house dust mites (HDM) for 60 days to become allergic asthma model mice, and a group of HDM-treated asthma model mice were treated with DEX. HDM-treated asthma model mice exhibited increased airway hyperresponsiveness (AHR) and inflammatory infiltration in lung tissue. An elevated level of IL-4, IL-5, and TNF-α was detected in bronchoalveolar lavage fluid (BALF) by Luminex liquid suspension chip. Asthma model mice also presented memory deficits accompanied with morphological changes at the synaptic levels in the cortex and hippocampus. Meanwhile, vascular edema and increased expression of HIF-1α and HIF-2α were found in the brain of asthma model mice. Interestingly, DEX treatment could reverse the inflammatory changes in asthma model mice airway, rescue the cognitive impairment and improve the synaptic plasticity. Besides, DEX significantly decreased the expression of HIF-1α and HIF-2α in mice brain and lung. These processes may be used to decipher the complex interplay and pathological changes between asthma and cognition. This study provides laboratory evidence for the prevention and treatment of cognitive malfunction induced by asthma.

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Role of metalloproteinases and TNF-α in obesity-associated asthma in mice

Cited by 15 publications

References 46 publications

Network Pharmacology Analysis of the Identification of Phytochemicals and Therapeutic Mechanisms of Paeoniae Radix Alba for the Treatment of Asthma

Network Pharmacology Analysis of the Identification of Phytochemicals and Therapeutic Mechanisms of Paeoniae Radix Alba for the Treatment of Asthma

Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice

Allergic Asthma-Induced Cognitive Impairment is Alleviated by Dexamethasone

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