Epithelium-derived chemokines induce airway smooth muscle cell migration.
ABSTRACT The remodelling of airway smooth muscle (ASM) associated with asthma severity may involve the migration of ASM cells towards the epithelium. However, little is known about the mechanisms of cell migration and the effect of epithelial-derived mediators on this process.
The main objective of the current study is to assess the effects of epithelial-derived chemokines on ASM cell migration.
Normal human ASM cells were incubated with supernatants from cells of the bronchial epithelial cell line BEAS-2B and normal human bronchial epithelial (NHBE) cells. To induce chemokine production, epithelial cells were treated with TNF-alpha. Chemokine expression by epithelial cells was evaluated by quantitative real-time PCR, ELISA and membrane antibody array. To identify the role of individual chemokines in ASM cell migration, we performed migration assays with a modified Boyden chamber using specific neutralizing antibodies to block chemokine effects.
Supernatants from BEAS-2B cells treated with TNF-alpha increased ASM cell migration; migration was increased 1.6 and 2.5-fold by supernatant from BEAS-2B cells treated with 10 and 100 ng/mL TNF-alpha, respectively. Protein levels in supernatants and mRNA expression by BEAS-2B cells of regulated on activation, normal T cell expressed and secreted (RANTES) and IL-8 were significantly increased by 100 ng/mL TNF-alpha treatment. The incubation of supernatant with antibodies to RANTES or IL-8 significantly reduced ASM cell migration, and the combined antibodies further inhibited the cell migration. The migratory effects of supernatants and inhibiting effects of RANTES and/or IL-8 were confirmed also using NHBE cells.
The results show that chemokines from airway epithelial cells cause ASM cell migration and might potentially play a role in the process of airway remodelling in asthma.
Article: Remodeling in asthma.[Show abstract] [Hide abstract]
ABSTRACT: Airway remodeling encompasses the structural alterations in asthmatic compared with normal airways. Airway remodeling in asthmatic patients involves a wide array of pathophysiologic features, including epithelial changes, increased smooth muscle mass, increased numbers of activated fibroblasts/myofibroblasts, subepithelial fibrosis, and vascular changes. Multiple cytokines, chemokines, and growth factors released from both inflammatory and structural cells in the airway tissue create a complex signaling environment that drives these structural changes. However, recent investigations have changed our understanding of asthma from a purely inflammatory disease to a disease in which both inflammatory and structural components are equally involved. Several reports have suggested that asthma primarily develops because of serious defects in the epithelial layer that allow environmental allergens, microorganisms, and toxins greater access to the airway tissue and that can also stimulate the release of mediators from the epithelium, thus contributing to tissue remodeling. Lung-resident fibroblasts and smooth muscle cells have also been implicated in the pathogenesis of airway remodeling. Remodeling is assumed to result in persistent airflow limitation, a decrease in lung function, and airway hyperresponsiveness. Asthmatic subjects experience an accelerated decrease in lung function compared with healthy subjects, which is proportionally related to the duration and severity of their disease.The Journal of allergy and clinical immunology 05/2011; 128(3):451-62; quiz 463-4. · 12.05 Impact Factor
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ABSTRACT: Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR. The mechanisms of AHR in asthma may involve a larger release of contractile mediators and/or a lower release of relaxant mediators, an improved ASM cell excitation/contraction coupling, and/or an alteration in the contraction/load coupling. Beyond its contractile function, ASM is also involved in bronchial inflammation and remodelling. Whereas ASM is a target of the inflammatory process, it can also display proinflammatory and immunomodulatory functions, through its synthetic properties and the expression of a wide range of cell surface molecules. ASM remodelling represents a key feature of asthmatic bronchial remodelling. ASM also plays a role in promoting complementary airway structural alterations, in particular by its synthetic function.Journal of Allergy 01/2011; 2011:742710.
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ABSTRACT: In this paper, we propose a new, fast, and stable hybrid numerical method for multiphase image segmentation using a phase-field model. The proposed model is based on the Allen–Cahn equation with a multiple well potential and a data-fitting term. The model is computationally superior to the previous multiphase image segmentation via Modica-Mortola phase transition and a fitting term. We split its numerical solution algorithm into linear and a nonlinear equations. The linear equation is discretized using an implicit scheme and the resulting discrete system of equations is solved by a fast numerical method such as a multigrid method. The nonlinear equation is solved analytically due to the availability of a closed-form solution. We also propose an initialization algorithm based on the target objects for the fast image segmentation. Finally, various numerical experiments on real and synthetic images with noises are presented to demonstrate the efficiency and robustness of the proposed model and the numerical method.Computers & Mathematics with Applications. 01/2011; 62:737-745.