MFG‐E8/integrin β3 signaling contributes to airway inflammation response and airway remodeling in an ovalbumin‐induced murine model of asthma

Zhi, Yueli; Huang, Han; Liang, Lihong

doi:10.1002/jcb.27142

Cited by 8 publications

(4 citation statements)

References 31 publications

(64 reference statements)

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“…Increasing infiltration of leukocytes around the airway, particularly eosinophils, is one of the main factors in the pathogenesis of asthma ( 36 ). The present study demonstrated that DEX effectively decreased inflammatory cell infiltration in the airway and inhibited mucus overproduction in OVA-induced asthmatic mice.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

et al. 2022

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Dexmedetomidine (DEX) suppresses inflammatory responses and protects against organ injury. The aim of the present study was to investigate the effect of DEX on airway hyperresponsiveness (AHR) and allergic airway inflammation, as well as its underlying mechanism of action in a murine model of ovalbumin (OVA)-induced asthma. A total of 30 female BALB/c mice were divided into 6 groups (n=5 mice/group): Control, OVA, OVA + DEX (20, 30 or 50 µg/kg) and OVA + TAK-242 [a toll-like receptor 4 (TLR4) inhibitor]. The mice were intraperitoneally injected with 20, 30 or 50 µg/kg DEX 1 h before OVA challenge. AHR to inhaled methacholine (Mch) was measured, and the mice were sacrificed 24 h after the last challenge. AHR following Mch inhalation was measured using the FlexiVent apparatus. Hematoxylin and eosin, periodic acid-Schiff and Wright-Giemsa staining was performed to evaluate inflammatory cell infiltration in the lung tissue. The levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid were analyzed using ELISA, and their mRNA expression levels in the lung tissue were examined using reverse transcription-quantitative PCR. The protein expression of TLR4, NF-κB and phosphorylated (p) NF-κB in the lung tissue was also detected using immunohistochemistry. In the murine OVA-induced asthma model, DEX decreased AHR following Mch inhalation and reduced the infiltration of inflammatory cells. IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluid were significantly lower following DEX treatment. Furthermore, DEX treatment inhibited the expression of TLR4, NF-κB and p-NF-κB in the lung tissue and exhibited a similar effect to TAK-242 treatment. In conclusion, DEX may attenuate AHR and allergic airway inflammation by inhibiting the TLR4/NF-κB pathway. These results suggested that DEX may represent a potential anti-inflammatory agent for the treatment and management of patients with asthma.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

et al. 2022

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“… 68 , 69 Conversely, interactions between Mfge8 and integrin β3 subunits protect against allergen induced airway remodeling changes, including goblet cell hyperplasia. 70 …”

Section: Epithelial Changes In Airway Remodelingmentioning

confidence: 99%

Pathobiology of Airway Remodeling in Asthma: The Emerging Role of Integrins

Joseph¹,

Tatler²

2022

JAA

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Airway remodeling is a complex clinical feature of asthma that involves long-term disruption and modification of airway architecture, which contributes significantly to airway hyperresponsiveness (AHR) and lung function decline. It is characterized by thickening of the airway smooth muscle layer, deposition of a matrix below the airway epithelium, resulting in subepithelial fibrosis, changes within the airway epithelium, leading to disruption of the barrier, and excessive mucous production and angiogenesis within the airway wall. Airway remodeling contributes to stiffer and less compliant airways in asthma and leads to persistent, irreversible airflow obstruction. Current asthma treatments aim to reduce airway inflammation and exacerbations but none are targeted towards airway remodeling. Inhibiting the development of airway remodeling or reversing established remodeling has the potential to dramatically improve symptoms and disease burden in asthmatic patients. Integrins are a family of transmembrane heterodimeric proteins that serve as the primary receptors for extracellular matrix (ECM) components, mediating cell–cell and cell–ECM interactions to initiate intracellular signaling cascades. Cells present within the lungs, including structural and inflammatory cells, express a wide and varying range of integrin heterodimer combinations and permutations. Integrins are emerging as an important regulator of inflammation, repair, remodeling, and fibrosis in the lung, particularly in chronic lung diseases such as asthma. Here, we provide a comprehensive summary of the current state of knowledge on integrins in the asthmatic airway and how these integrins promote the remodeling process, and emphasize their potential involvement in airway disease.

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“…Thus, β3 may serve as a putative therapeutic target in ameliorating sepsis (Chen et al, 2020). In an ovalbumin-induced asthma murine model, administration of recombinant milk fat globule epidermal growth factor 8 (MFG-E8) suppressed both lung inflammation and airway remodeling by binding with its receptor integrin β3 (Zhi et al, 2018). It has been shown that integrin αMβ2 is essential for the adherence of neutrophils to endothelial cells as well as for transmigration (Hahm et al, 2013).…”

Section: Integrins In Health and Disease I: Inflammationmentioning

confidence: 99%

Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights Into the Multifaceted Roles of an Emerging Ligand Irisin

Park

Myint

Ito

et al. 2020

Front. Cell Dev. Biol.

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Integrins are transmembrane proteins that mediate cellular adhesion and migration to neighboring cells or the extracellular matrix, which is essential for cells to undertake diverse physiological and pathological pathways. For integrin activation and ligand binding, bidirectional signaling across the cell membrane is needed. Integrins aberrantly activated under pathologic conditions facilitate cellular infiltration into tissues, thereby causing inflammatory or tumorigenic progressions. Thus, integrins have emerged to the forefront as promising targets for developing therapeutics to treat autoimmune and cancer diseases. In contrast, it remains a fact that integrin-ligand interactions are beneficial for improving the health status of different tissues. Among these ligands, irisin, a myokine produced mainly by skeletal muscles in an exercise-dependent manner, has been shown to bind to integrin αVβ5, alleviating symptoms under unfavorable conditions. These findings may provide insights into some of the underlying mechanisms by which exercise improves quality of life. This review will discuss the current understanding of integrin-ligand interactions in both health and disease. Likewise, we not only explain how diverse ligands play different roles in mediating cellular functions under both conditions via their interactions with integrins, but also specifically highlight the potential roles of the emerging ligand irisin in inflammation, cancer, and metabolic disease.

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MFG‐E8/integrin β3 signaling contributes to airway inflammation response and airway remodeling in an ovalbumin‐induced murine model of asthma

Cited by 8 publications

References 31 publications

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF‑κB signaling pathway in mice

Pathobiology of Airway Remodeling in Asthma: The Emerging Role of Integrins

Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights Into the Multifaceted Roles of an Emerging Ligand Irisin

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