Transplacental passage of interleukins 4 and 13?
The mechanisms by which prenatal events affect development of adult disease are incompletely characterized. Based on findings in a murine model of maternal transmission of asthma risk, we sought to test the role of the pro-asthmatic cytokines interleukin IL-4 and -13. To assess transplacental passage of functional cytokines, we assayed phosphorylation of STAT-6, a marker of IL-4 and -13 signaling via heterodimeric receptor complexes which require an IL-4 receptor alpha subunit. IL-4 receptor alpha-/- females were mated to wild-type males, and pregnant females were injected with supraphysiologic doses of IL-4 or 13. One hour after injection, the receptor heterozygotic embryos were harvested and tissue nuclear proteins extracts assayed for phosphorylation of STAT-6 by Western blot. While direct injection of embryos produced a robust positive control, no phosphorylation was seen after maternal injection with either IL-4 or -13, indicating that neither crossed the placenta in detectable amounts. The data demonstrate a useful approach to assay for transplacental passage of functional maternal molecules, and indicate that molecules other than IL-4 and IL-13 may mediate transplacental effects in maternal transmission of asthma risk.
Lim
Robert H
RH
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA. rlim@hsph.harvard.edu
Kobzik
Lester
L
D000818:Animals; D015153:Blotting, Western; D005260:Female; D018793:Interleukin-13 / Q000008:administration & dosage / Q000378:metabolism*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000378:metabolism*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D050800:STAT6 Transcription Factor / Q000378:metabolism
D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D009687:Nuclear Proteins; D050800:STAT6 Transcription Factor; D015847:Interleukin-4