Maternal IL-1β Production Prevents Lung Injury in a Mouse Model of Bronchopulmonary Dysplasia

Autor: Erica Bäckström, Kristina Bry, Urpo Lappalainen
Rok vydání: 2010
Předmět:
Zdroj: American Journal of Respiratory Cell and Molecular Biology. 42:149-160
ISSN: 1535-4989
1044-1549
DOI: 10.1165/rcmb.2008-0287oc
Popis: Little is known about the influence of maternal inflammation on neonatal outcome. Production of IL-1beta in the lungs of newborn infants is associated with bronchopulmonary dysplasia. Using bitransgenic (bi-TG) mice in which human (h) IL-1beta is expressed with a doxycycline-inducible system controlled by the Clara cell secretory protein promoter, we have shown that hIL-1beta expression causes a bronchopulmonary dysplasia-like illness in infant mice. To study the hypothesis that maternal hIL-1beta production modifies the response of the newborn to hIL-1beta, doxycycline was administered to bi-TG and control dams from Embryonic Day 0, inducing production of hIL-1beta by the bi-TG dams before hIL-1beta production started in their bi-TG fetuses, or from Embryonic Day 15, inducing simultaneous production of hIL-1beta by both the bi-TG dams and their bi-TG fetuses. In addition to the lungs, hIL-1beta was expressed at low levels in the uteri of bi-TG dams. Maternal inflammation preceding fetal inflammation increased the survival and growth of hIL-1beta-expressing pups, enhanced alveolarization, and protected the airways against remodeling and goblet cell hyperplasia. Maternal hIL-1beta production preceding fetal hIL-1beta production caused silencing of several inflammatory genes, including CXC and CC chemokines, murine IL-1beta, serum amyloid A3, and Toll-like receptors 2 and 4, and suppressed the expression of chitinase-like lectins Ym1 and Ym2 in the lungs of infant mice. Maternal inflammation protects the newborn against subsequent hIL-1beta-induced lung inflammation and injury. In contrast, induction of hIL-1beta production simultaneously in bi-TG dams and their fetuses offered no protection against inflammatory lung disease in the neonate.
Databáze: OpenAIRE