Transforming growth factor beta 1 (TGF beta 1) gene expression by eosinophils in asthmatic airway inflammation.

Abstract

The increase in thickness of bronchial walls by such structural changes as subepithelial fibrosis contributes to the severity and chronicity of asthma by amplifying airway narrowing. However, the pathogenesis of this structural alteration is not known. Transforming growth factor beta 1 (TGF beta 1) is known to have biologic activities relevant to the cellular and molecular events in subepithelial fibrosis, such as the deposition of collagen I and III and the increase of myofibroblasts beneath the epithelial basement membrane. Therefore, we examined TGF beta 1 gene expression in bronchial biopsy tissues from five severe asthmatics, five mild asthmatics, and five normal subjects using in situ hybridization combined with histochemical staining. Cells expressing TGF beta 1 mRNA were detected in tissues from four normal subjects, one mild asthmatic, and five severe asthmatics. The density of positive cells in severe asthmatic tissues (52.1 +/- 22.7, mean +/- SD/mm2) was significantly greater than that in mild asthmatic tissues (1.0 +/- 1.9/mm2, P < 0.01) or normal tissues (10.5 +/- 10.6/mm2, P < 0.02). The density in mild asthmatic tissues was not significantly different from that in normal tissues. The vast majority of positive cells in severe (99.1 +/- 1.7%) and mild (100%) asthmatic tissues were identified as eosinophils. In contrast, eosinophils constituted a small portion of positive cells (20.8 +/- 21.6%) in normal tissues. These results indicated that TGF beta 1 mRNA was overexpressed in severe asthmatics and that the main source of the mRNA was eosinophils, suggesting that eosinophils play an important role in the pathogenesis not only of inflammation but also of structural changes, such as subepithelial fibrosis, in asthmatic airways.

Peroxisome proliferator–activated receptor γ is expressed in airways and inhibits features of airway remodeling in a mouse asthma model☆

“…2,6,7,33 Smad proteins, c-Jun NH2-terminal kinase, and mitogen-activated protein kinase are reported to be involved in TGF-b signaling. 33,34 These factors are targets for PPAR-c regulation.…”

“…5 In most studies TGF-b expression correlates with basement membrane thickness, fibroblast numbers, and disease severity. 2,6,7 Nuclear receptors are ligand-activated transcription factors. 8 The glucocorticoid receptor a (GR-a) mediates the anti-inflammatory effects of corticosteroids.…”

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

“…In human asthma, activated eosinophils are a major source of TGF-␤1 by in situ hybridization (19) and immunohistochemistry (20). Isolated human eosinophils produce both TGF-␤1 protein (39) and TGF-␤1 bioactivity (40).…”

“…Indeed, in addition to their conventional effector functions, which are based on the release of lipid mediators and cationic granule proteins, eosinophils may functionally interact with immune cells or interstitial cells by presenting Ags (17) and producing cytokines (e.g., IL-4) and growth factors (e.g., TGF-␤) (18). In particular, the association between human eosinophils and TGF-␤1, a factor involved in immunoregulation and wound healing, has been studied extensively in patients with asthma (19,20) and atopic dermatitis (21).…”

A water extract of Samchulkunbi-tang attenuates airway inflammation by inhibiting inos and MMP-9 activities in an ovalbumin-induced murine asthma model

“…Another important aspect of asthma is that the matrix metalloproteinase-9 (MMP-9) level increases significantly in the bronchoalveolar lavage fluid (BALF), blood, and sputum of people with asthma [10]. MMP-9 belongs to a family of extracellular proteases that are responsible for the degradation of the extracellular matrix during tissue remodeling [11]. Therefore, the control of nitric oxide synthase (NOS) and MMP-9 activities is an important aspect of asthma treatment.…”