transforming-growth-factor-beta and Bronchiectasis

Clubbing was first described by Hippocrates more than 2.500 years ago. It may be seen alone or as part of an entity called hypertrophic osteoarthropathy which include periostitis, arthritis and sometimes thickening and edema of the skin around the affected joints. Pulmonary diseases such as cancer, abscess, empyema, bronchiectasis and cystic fibrosis are the major diseases known to be associate with hypertrophic osteoarthropathy. Digestive tract cancer, cyanogenic congenital heart disease are well known association. Many theories have attempted to explain the appearance of this sign but few have persisted. In this article, we review characteristics, relation with etiology and the basis of the pathophysiology of hypertrophic osteoarthropathy and particularly of clubbing.

Topics: Bronchiectasis; Causality; Cystic Fibrosis; Digestive System Neoplasms; Empyema; Ferritins; Heart Defects, Congenital; Humans; Lung Abscess; Lung Neoplasms; Osteoarthropathy, Secondary Hypertrophic; Platelet-Derived Growth Factor; Prostaglandins; Transforming Growth Factor beta

Bronchiectasis is a chronic inflammatory and infective airway disease characterized by irreversible dilatation of the bronchi and persistent purulent sputum. Transforming growth factor-beta(1) (TGF-beta(1)) has been found to be increased in the lungs or bronchoalveolar lavage fluid of patients with inflammatory lung diseases. However, little is known on the serum TGF-beta(1) levels in patients with bronchiectasis. We aimed to determine the serum TGF-beta(1) concentrations in 95 patients with stable bronchiectasis (63 women; mean+/-sd age, 58.9+/-14.1 years) and 68 control subjects (23 women; 48.9+/-12.8 years) by ELISA, and to correlate with clinical parameters. The serum TGF-beta(1) levels were significantly higher in bronchiectatic patients compared with control subjects (median [range], 1812.5 pg/ml [1226.4-4114.5 pg/ml] vs. 1342.4 pg/ml [940.3-2371.7 pg/ml]; P<0.001). There was, however, no correlation between serum TGF-beta(1) levels with FEV(1) (% predicted), FVC (% predicted), 24h sputum volume, the number of bronchiectatic lung lobes or total white blood cell count (P>0.05). Our findings support previous indications that TGF-beta(1) may contribute to bronchiectatic airway inflammation. Further studies on the potential mechanisms and pathogenesis implications of this elevation should also be pursued in future.

Topics: Adult; Aged; Bronchiectasis; Case-Control Studies; China; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Transforming Growth Factor beta; Transforming Growth Factor beta1

During pulmonary development, Sonic hedgehog (Shh) and transforming growth factor beta1 (TGF-beta1) signalling both contribute to branching morphogenesis. In interstitial lung disease, the complex alveolar structure of the lung is disrupted and remodelled, which leads to fibrosis, loss of respiratory surface, morbidity, and mortality. It is well documented that TGF-beta1 is involved in fibrosis. However, little is known about Shh signalling in damaged epithelia. This study examined whether or not components of the Shh signalling pathway, as well as TGF-beta1, are expressed in human fibrotic lung disease (cryptogenic fibrosing alveolitis and bronchiectasis) and in murine experimental models of fibrotic and non-fibrotic chronic pulmonary inflammation. Using immunohistochemistry, it was observed that Shh, like TGF-beta1, is up-regulated in epithelial cells at sites of fibrotic disease but not non-fibrotic inflammation. The Shh receptor patched was detected in infiltrating mononuclear cells and alveolar macrophages, as well as normal resting peripheral blood T lymphocytes. Neither Shh nor patched is expressed by hyperproliferative goblet cells in inflammatory epithelium. This study demonstrates that patched is present in human peripheral CD4 and CD8 lymphocytes at both protein and mRNA levels. Taken together, these results suggest that components of the highly conserved Shh signalling pathway may play a role in the remodelling of damaged pulmonary epithelium and that damaged epithelium and cells of the immune system may communicate via this pathway.

Topics: Animals; Antigens, Dermatophagoides; Arthropod Proteins; Bronchiectasis; Chronic Disease; Cysteine Endopeptidases; Female; Hedgehog Proteins; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Patched Receptors; Patched-1 Receptor; Pneumonia; Pulmonary Fibrosis; Receptors, Cell Surface; Respiratory Hypersensitivity; RNA, Messenger; Signal Transduction; T-Lymphocyte Subsets; Trans-Activators; Transforming Growth Factor beta; Transforming Growth Factor beta1; Up-Regulation