Maternal IL-1beta production prevents lung injury in a mouse model of bronchopulmonary dysplasia.
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.
Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden.
Erica
E
Bäckström
Urpo
U
Lappalainen
Kristina
K
Bry
D055371:Acute Lung Injury / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001997:Bronchopulmonary Dysplasia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
D017931:DNA Primers; D053583:Interleukin-1beta; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004318:Doxycycline