Asthma fibroblasts

According to current thinking, epithelial dysfunction, either intrinsic to asthma or caused by persistent inflammation, leads to epithelial release of profibrotic cytokines such as epidermal growth factor and TGF-P acting on fibroblasts and smooth muscle cells, disturbing the equilibrium... 

Pierzchalska, M., Szabo, Z., Sanak, M., Soja, J., and Szczekhk, A. (2003) Deficient prostaglandin E-2 production by bronchial fibroblasts of asthmatic patients, with special reference to aspirin-induced asthma. J. Allergy Clin. Immunol. Ill, 1041-1048. 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

In asthma, all cells of the airways are involved and become activated (Fig. 26-2). Included are eosinophils, T cells, mast cells, macrophages, epithelial cells, fibroblasts, and bronchial smooth muscle cells. These cells also regulate airway inflammation and initiate the process of remodeling by the release of cytokines and growth factors. ... 

Fibroblasts are found frequently in connective tissue. Human lung fibroblasts may behave as inflammatory cells on activation by IL-4 and IL-13. The myofibroblast may contribute to the regulation of inflammation via the release of cytokines and to tissue remodeling. In asthma, myofibroblasts are increased in numbers beneath the reticular basement membrane, and there is an association between their numbers and the thickness of the reticular basement membrane. ... 

Thromboxane A2 is produced by alveolar macrophages, fibroblasts, epithelial cells, neutrophils, and platelets within the lung. Indirect evidence from animal models suggests that thromboxane A2 may have several effects, including bronchoconstriction, involvement in the late asthmatic response, and involvement in the development of airway inflammation and BHR. Potent and specific thromboxane synthetase inhibitors will be crucial tools for understanding the role of thromboxanes in asthma. 

Also from studies of physiological airway repair, it is well known that the interaction between epithelium and mesenchymal elements such as fibroblasts is essential, and an abnormal response of this epithelial-mesenchymal trophic unit has been proposed to be central to the airway pathology and physiology characteristic of asthma [47]. 

Other applications of pH-responsive polymers for drug-delivery systems have also been explored such as the incorporation of fibroblast growth factors to improve angiogenesis in infracted myocardium (Garbem et al., 2011) the incorporation of ketoprofen for colon-targeted delivery (Kulkami et al., 2012) intracellular delivery of ovalbumin to dendritic cells (a class of cells intimately involved with adaptive immunity) (Hn et al., 2007) and for controlling drug release in nocturnal asthma treatment (Tran et al., 2013). 

Asthma has been traditionally viewed as a chronic inflammatory condition characterized by airway infiltration by activated mast cells and eosinophils, orchestrated by specific Th2-type T lymphocytes (24). However, neutrophils have recently been implicated in more severe forms of asthma, and it is also increasingly evident that the bronchial epithelium, endothelium, fibroblasts, and the extracellular matrix play a dynamic role in the airway inflammation of asthma (Fig. 2). 

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