Bioactive Transforming Growth Factor-Beta in the Lungs of Extremely Low Birthweight Neonates Predicts the Need for Home Oxygen Supplementation

Abstract

Transforming growth factor-β (TGF-β) is a peptide implicated in tissue injury and repair but its role in the premature human lung remains unclear. In the present study, we used a TGF-β responsive-promoter-luciferase construct in mink lung epithelial cells to quantify levels of biologically active TGF-β (BA-TGF-β) in the endotracheal aspirate (ETA) fluid from 16 extremely low birthweight neonates [6 M/10 F, mean GA 26 weeks (range 23–30), mean BW 774 g (range 555–1,075)]. ETA fluid was obtained on day 1 and then every 4 days up to 32 days. BA-TGF-β levels were low (92 ± 19 pg/ml) in the first 24 h of life and then increased 5- to 10-fold with peak BA-TGF-β levels (400 ± 50 pg/ml) on day 20–25. BA-TGF-β levels were higher in male than female infants (p = 0.0056). Prenatal steroids decreased significantly the amount of BA-TGF-β recovered. High initial levels of BA-TGF-β persisted over time and were predictive of the need for oxygen therapy at home. We conclude that abundant BA- TGF-β is present in the lungs of preterm infants and speculate that it may be involved in inflammatory and repair processes encountered in acute and chronic lung disease.

Inhibition of phosphodiesterase 4 enhances lung alveolarisation in neonatal mice exposed to hyperoxia

“…Transforming growth factor (TGF)-b has a well documented role in late lung development [36]; however, TGF-b signalling is dysregulated in BPD, both in human patients [37], as well as in hyperoxia-induced BPD in rodents [24]. Interestingly, PDE4 inhibitors are potent antagonists of TGF-b signalling, since roflumilast antagonises the induction of connective tissue growth factor, collagen I and fibronectin by TGF-b in human airway smooth muscle cells [38].…”

Apoptosis in Lung Development and Neonatal Lung Injury

“…Furthermore, TGF-␤1 induces apoptosis in human lung epithelial lines (80) and enhances Fas-FasLmediated apoptosis via caspase 3 activation and downregulation of p21 expression, a cyclin-dependent kinase inhibitor, both in vitro (81) and in vivo (77). Increased levels of TGF-␤1 are found in airway lavage samples of infants in the early stages of BPD (68). Moreover, high levels of TGF-␤1 are associated with more severe cases of BPD (68).…”

“…Increased levels of TGF-␤1 are found in airway lavage samples of infants in the early stages of BPD (68). Moreover, high levels of TGF-␤1 are associated with more severe cases of BPD (68). To date, the expression of FasL in infants with BPD has not been examined.…”

Pulmonary inflammation and bronchopulmonary dysplasia

“…76 In preterm infants with BPD, increased levels of TGF-b have been detected in the airway secretions. [77][78][79] Using the data of the inhibitory effects of TGF-b levels on normal lung development, it can be speculated that interference of this cytokine with lung growth and suboptimal levels of different growth factors may also add to the pathogenesis of 'new BPD' and its possible long-term consequences. In fact, low airway concentrations of keratinocyte growth factor and hepatocyte growth factor were found to be associated with more severe lung disease in preterm infants.…”