Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Chung, Kian Fan

doi:10.1034/j.1399-3003.2000.15e26.x

Cited by 130 publications

(95 citation statements)

References 78 publications

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“…Both the secretory and contractile phenotypes have the potential to influence the severity of asthma, by promoting airway remodelling or bronchospasm, respectively. ASM has the capacity to synthesize and release pro-inflammatory molecules such as eotaxin and regulated on activation, normal T-cell expressed and secreted (reviewed elsewhere in this series by CHUNG [38]), both noted for their eosinophil chemoattractant properties, although formal proof that ASM is involved in the promotion of inflammation is lacking.…”

Section: Mathematical Models Of Airway Narrowingmentioning

confidence: 99%

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

2000

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Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass.Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASM, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM.Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin light chain kinase activity. Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined. Eur Respir J 2000; 16: 349±354.

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Section: Mathematical Models Of Airway Narrowingmentioning

confidence: 99%

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

2000

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“…[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35], and procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (8th Edition, 2011). Details regarding the generation and characterization of PLA 2 R 2/2 mice (systemically deficient in PLA 2 R) were described previously (25,26).…”

Section: Micementioning

confidence: 99%

Deficiency of Phospholipase A2 Receptor Exacerbates Ovalbumin-Induced Lung Inflammation

Tamaru

Mishina

Watanabe

et al. 2013

The Journal of Immunology

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Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R−/−) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R+/+) mice, PLA2R−/− mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R−/− mice, intratracheally instilled [125I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R+/+ mice. The degradation of the instilled [125I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R−/− mice than in PLA2R+/+ mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.

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“…ASMC express adhesion molecules and synthesize many cytokines and chemokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, eotaxin, and RANTES. These mediators are critically implicated in the recruitment, survival, and activation of key effector cells, such as eosinophils, neutrophils, and T lymphocytes, in asthma and COPD (10).…”

mentioning

confidence: 99%

Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

Sukkar

Issa

Xie

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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mokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX 3C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX3CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1␤, TNF-␣, and IFN-␥, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-␤. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-␥ and TNF-␣ induced FKN mRNA and protein expression in a time-and concentration-dependent manner. TGF-␤ had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10 Ϫ8 -10 Ϫ6 M) significantly upregulated cytokineinduced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH2-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 M) and SB-203580 (20 M), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-␥-and TNF-␣-induced JNK phosphorylation remained unaltered in the presence of TGF-␤ but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-␤-or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors. chemokine; airway inflammation; asthma; chronic obstructive pulmonary disease THERE IS NOW SUBSTANTIAL EVIDENCE suggesting that airway smooth muscle cells (ASMC), by virtue of their immunomodulatory functions, may be involved in regulating airway inflammatory responses in diseases such as asthma and chronic obstructive pulmonary disease (COPD). ASMC express adhesion molecules and synthesize many cytokines and chemokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, eotaxin, and RANTES. These mediators are critically implicated in the recruitment, survival, and activation of key effector cells, such as eosinophils, neutrophils, and T lymphocytes, in asthma and COPD (10).Fractalkine (FKN), also known as CX 3 C ligand 1 (CX 3 CL1), is a novel chemokine belonging to the CX 3 C chemokine family. FKN is a multidomain molecule expressed on the cell surface and consists of a transmembrane region and a heavily glycosylated mucin-like stalk that extends from the cell surface, holding the chemokine domain at its tip (5). FKN also exists as a soluble glycoprotein that is generated by proteolytic cleavage of the full-length molecule at a membrane-proximal site (27,32,55). The physiological relevance of membrane and soluble FKN is not known; however, it is cu...

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Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Cited by 130 publications

References 78 publications

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

Deficiency of Phospholipase A2 Receptor Exacerbates Ovalbumin-Induced Lung Inflammation

Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

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Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

Cited by 130 publications

References 78 publications

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

Deficiency of Phospholipase A2 Receptor Exacerbates Ovalbumin-Induced Lung Inflammation

Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

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Fractalkine/CX₃CL1 production by human airway smooth muscle cells: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids