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The role of IL‐6 and IL‐11 in hyperoxic injury in developing lung
Author(s) -
Chetty Anne,
Cao GongJee,
Manzo Nicholas,
Nielsen Heber C,
Waxman Aaron
Publication year - 2008
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.20777
Subject(s) - hyperoxia , tunel assay , room air distribution , medicine , lung , apoptosis , andrology , in vivo , interleukin , endocrinology , cytokine , pathology , biology , immunohistochemistry , biochemistry , physics , microbiology and biotechnology , thermodynamics
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. Pediatr Pulmonol. 2008; 43:297–304. © 2008 Wiley‐Liss, Inc.