Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts

Cell‐cell signaling roles for reactive oxygen species (ROS) generated in response to growth factors/cytokines in nonphagocytic cells are not well defined. In this study, we show that fibroblasts isolated from lungs of patients with idiopathic pulmonary fibrosis (IPF) generate extracellular hydrogen peroxide (H2O2) in response to the multifunctional cytokine, transforming growth factor‐β1 (TGF‐β1). In contrast, TGF‐β1 stimulation of small airway epithelial cells (SAECs) does not result in detectable levels of extracellular H2O2. IPF fibroblasts independently stimulated with TGF‐β1 induce loss of viability and death of overlying SAECs when cocultured in a compartmentalized Transwell system. These effects on SAECs are inhibited by the addition of catalase to the coculture system or by the selective enzymatic blockade of H2O2 production by IPF fibroblasts. IPF fibroblasts heterogeneously express α‐smooth muscle actin stress fibers, a marker of myofibroblast differentiation. Cellular localization of H2O2 by a fluorescent‐labeling strategy demonstrated that extracellular secretion of H2O2 is specific to the myofibroblast phenotype. Thus, myofibroblast secretion of H2O2 functions as a diffusible death signal for lung epithelial cells. This novel mechanism for intercellular ROS signaling may be important in physiological/pathophysiological processes characterized by regenerating epithelial cells and activated myofibroblasts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154383/1/fsb2fj042882fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154383/2/fsb2fj042882fje-sup-0001.pd

Relationship between breast-feeding and adiposity in infants and pre-school children

Objectives: We aimed to establish associations of duration of breast-feeding with mean BMI and waist circumference, as well as the likelihood of being overweight/ obese, during early childhood. Design: Cross-sectional, population-based study. Height, weight and waist circumference were measured and BMI calculated. Interviewer-administered questionnaire determined whether the child was ever breast-fed and the duration of breast-feeding. Setting: Sydney, Australia. Subjects: Infants and pre-school children (n 2092) aged 1-6 years were examined in the Sydney Paediatric Eye Disease Study during 2007-2009. Results: Of the children aged 1-6 years, 1270 had been breast-fed compared with 822 who were never breast-fed. After multivariable adjustment, 1-6-year-old children who were ever breast-fed compared with those who were not had significantly lower BMI, 16.7 (SE 0.1) kg/m2 v. 17.1 (SE 0.2) kg/m2 (P=0.01). Decreasing BMI was associated with increasing duration of breast-feeding (Ptrend=0.002). After multivariable adjustment, each month increase in breastfeeding was associated with an average BMI decrease of 0.04 kg/m2 (P=0.002) and 0.03 kg/m2 (P=0.03) among children aged 1-2 years and 3-4 years, respectively. In 1-2-year-old children, each month increase in breast-feeding duration was associated with a 0.06cm decrease in waist circumference (P=0.04). Significant associations were not observed among 5-6-year-old children. Children who were ever breast-fed v. those never breast-fed were less likely to be overweight/obese (multivariable-adjusted OR=0.54; 95% CI 0.36, 0.83). Conclusions: We demonstrated a modest influence of breast-feeding on children\u27s BMI during early childhood, particularly among those aged less than 5 years