The role of IL-6 and IL-11 in hyperoxic injury in developing lung.
We examined the cytoprotective effect of interleukin-6 (IL-6) and interleukin-11 (IL-11) during oxidant injury in neonatal lung and the regulators of cell death in vitro and in vivo after oxidant exposure. Type II cells from day 21 fetal neonatal rat lungs were treated with varying concentrations of either IL-6 or IL-11 for 24 hr prior to exposure to H(2)O(2). Three-day-old transgenic lung-specific IL-11 and IL-6 overexpressing and wild type (WT) mouse pups were exposed to hyperoxia or room air for 3 days. Type II cells exposed to either IL-6 or IL-11 prior to oxidant injury exhibited improved survival compared to controls, 67% +/- 2.6 survivals in IL-6 pretreated cells compared to 48% +/- 1.6 in control; 63% +/- 3 survivals in IL-11 pretreated cells compared to 49% +/- 2.6 in control. The number of TUNEL positive cells in hyperoxia-exposed lungs was increased compared to room air animals (27 +/- 0.9 vs. 4 +/- 0.4; mean +/- SEM; P < 0.05). In contrast, the number of TUNEL positive cells was reduced in hyperoxia-exposed lungs from IL-11 (+) mice (15.2 +/- 2.2; mean +/- SEM; P < 0.05). There was an enhanced accumulation of Bcl-2 and reduction of Bax protein in hyperoxia-exposed IL-11 (+) compared to room air-exposed mice. This was not seen in hyperoxia-exposed IL-6 (+) pups. An increase in caspase-3 was seen in hyperoxia-exposed lungs of WT pups compared to IL-11 (+) pups. IL-11 and IL-6 provide protective effects against oxidant-mediated injury in fetal type II cells and IL-11 provides protection in vivo by down-regulation of caspase-mediated cell death.
Chetty
Anne
A
Department of Pediatrics, Floating Hospital for Children, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA. achetty@tufts-nemc.org
Cao
Gong-Jee
GJ
Manzo
Nicholas
N
Nielsen
Heber C
HC
Waxman
Aaron
A
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001997:Bronchopulmonary Dysplasia / Q000503:physiopathology*; D053148:Caspase 3 / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D018496:Hyperoxia / Q000276:immunology / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D017370:Interleukin-11 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000503:physiopathology; D051381:Rats
D017370:Interleukin-11; D015850:Interleukin-6; D053148:Caspase 3