Effects of Ureaplasma parvum lipoprotein multiple-banded antigen on pregnancy outcome in mice.
Ureaplasma spp. are members of the family Mycoplasmataceae and have been considered to be associated with chorioamnionitis and preterm delivery. However, it is unclear whether Ureaplasma spp. have virulence factors related to these manifestations. The purpose of the present study was to determine whether the immunogenic protein multiple-banded antigen (MBA) from Ureaplasma parvum is a virulence factor for preterm delivery. We partially purified MBA from a type strain and clinical isolates of U. parvum, and also synthesized a diacylated lipopeptide derived from U. parvum, UPM-1. Using luciferase assays, both MBA-rich fraction MRF and UPM-1 activated the NF-κB pathway via TLR2. UPM-1 upregulated IL-1β, IL-6, IL-12p35, TNF-α, MIP2, LIX, and iNOS in mouse peritoneal macrophage. MRF or UPM-1 was injected into uteri on day 15 of gestation on pregnant C3H/HeN mice. The intrauterine MRF injection group had a significantly higher incidence of intrauterine fetal death (IUFD; 38.5%) than the control group (14.0%). Interestingly, intrauterine injection of UPM-1 caused preterm deliveries at high concentration (80.0%). In contrast, a low concentration of UPM-1 induced a significantly higher rate of fetal deaths (55.2%) than the control group (14.0%). The placentas of the UPM-1 injection group showed neutrophil infiltration and increased iNOS protein expression. Our data indicate that MBA from the clinical isolate of U. parvum is a potential virulence factor for IUFD and preterm delivery in mice and that the N-terminal diacylated lipopeptide is essential for the initiation of inflammation.
Department of Developmental Medicine, Research Institute, Osaka Medical Center for Maternal and Child Health, 840-Murodo-cho, Izumi, Osaka 594-1101, Japan.
Kaoru
K
Uchida
Kumiko
K
Nakahira
Kazuya
K
Mimura
Takashi
T
Shimizu
Francesco
F
De Seta
Tetsu
T
Wakimoto
Yasuhiro
Y
Kawai
Makoto
M
Nomiyama
Koichi
K
Kuwano
Secondo
S
Guaschino
Itaru
I
Yanagihara
D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000302:isolation & purification; D045744:Cell Line, Tumor; D002821:Chorioamnionitis / Q000276:immunology*; D005260:Female; D005313:Fetal Death / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000302:isolation & purification; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014509:Ureaplasma / Q000276:immunology* / Q000472:pathogenicity; D016869:Ureaplasma Infections / Q000276:immunology*; D037521:Virulence Factors
D001426:Bacterial Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D010446:Peptide Fragments; D051195:Toll-Like Receptor 2; D037521:Virulence Factors; C089269:multiple-banded antigen, Ureaplasma
ANOVA; CAM; DMSO; GAPDH; H&E; IL; IUFD; KC; LIX; LPS-induced CXC chemokine; MBA; MIP2; MRF; Multiple-banded antigen; NF-κB; PBS; Preterm; RT-PCR; TLR; TNF; TX-114; Toll-like receptor; Toll-like receptor 2; Triton X-114; U. parvum; Ureaplasma parvum; analysis of variance; chorioamnionitis; dimethyl sulfoxide; glyceraldehyde-3-phosphate dehydrogenase; hematoxylin and eosin; iNOS; inducible nitric oxide synthase; interleukin; intrauterine fetal death; keratinocyte-derived chemokine; macrophage inflammatory protein 2; multiple-banded antigen; multiple-banded antigen rich fraction; nuclear factor kappa-light-chain-enhancer of activated B cells; phosphate buffered saline; rMBA; recombinant MBA; reverse transcription polymerase chain reaction; tumor necrosis factor