Distinct pathophysiologic pathways induced by in vitro infection and cigarette smoke in normal human fetal membranes.
OBJECTIVE
The purpose of this study was to document distinct pathways that are initiated by lipopolysaccharide and cigarette smoke stimulation of normal term fetal membranes.


METHODS
Fetal membranes from nonsmoking women at term, not in labor, from cesarean deliveries were placed in an organ explant system and stimulated with cigarette smoke extracts (CSEs), lipopolysaccharide, or lipopolysaccharide + CSE. Media were assayed for an interleukin (IL)-1beta, -1 receptor antagonist, -6, -8, -10, tumor necrosis factor alpha, soluble tumor necrosis factor receptors 1 and 2, and matrix metalloproteinases 1, 2, 3, 8, 9, and 12. Tissue homogenates were assayed for apoptotic markers (p53, caspase 3 activity, and cleaved poly [ADP-ribose] polymerase-1).


RESULTS
Lipopolysaccharide stimulation resulted in higher cytokine and matrix metalloproteinase concentrations, whereas it was lower after CSE and CSE + lipopolysaccharide stimulations, compared with control specimens. Apoptotic factors were several folds higher after CSE or CSE + lipopolysaccharide stimulation, compared with control specimens or lipopolysaccharide stimulations.


CONCLUSIONS
Cigarette smoke showed immunoinhibitory properties that potentially were mediated by apoptosis and lipopolysaccharide-induced proinflammatory response. This study demonstrated 2 independent pathophysiologic pathways that may alter pregnancy outcome.
Menon
Ramkumar
R
Perinatal Research Center, Centennial Women's Hospital, 2300 Patterson St,Nashville, TN 37203, USA. ymenon3@emory.edu
Fortunato
Stephen J
SJ
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002585:Cesarean Section; D016207:Cytokines / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D007239:Infections / Q000276:immunology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects*
D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; D020782:Matrix Metalloproteinases