PMID- 30764830
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20200225
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 16
IP  - 1
DP  - 2019 Feb 14
TI  - More than just inflammation: Ureaplasma species induce apoptosis in human brain 
      microvascular endothelial cells.
PG  - 38
LID - 10.1186/s12974-019-1413-8 [doi]
LID - 38
AB  - BACKGROUND: Ureaplasma species (spp.) are commonly regarded as low-virulent 
      commensals but may cause invasive diseases in immunocompromised adults and in 
      neonates, including neonatal meningitis. The interactions of Ureaplasma spp. with 
      host defense mechanisms are poorly understood. This study addressed 
      Ureaplasma-driven cell death, concentrating on apoptosis as well as inflammatory 
      cell death. METHODS: Human brain microvascular endothelial cells (HBMEC) were 
      exposed to Ureaplasma (U.) urealyticum serovar 8 (Uu8) and U. parvum serovar 3 
      (Up3). Resulting numbers of dead cells as well as mRNA levels and enzyme activity 
      of key agents in programmed cell death were assessed by flow cytometry, RNA 
      sequencing, and qRT-PCR, respectively. xCELLigence data were used for real-time 
      monitoring of changes in cell adhesion properties. RESULTS: Both Ureaplasma 
      isolates induced cell death (p < 0.05, vs. broth). Furthermore, Ureaplasma spp. 
      enhanced mRNA levels for genes in apoptosis, including caspase 3 (Up3 p < 0.05, 
      vs. broth), caspase 7 (p < 0.01), and caspase 9 (Up3 p < 0.01). Caspase 3 
      activity was increased upon Uu8 exposure (p < 0.01). Vice versa, Ureaplasma 
      isolates downregulated mRNA levels for proteins involved in inflammatory cell 
      death, namely caspase 1 (Uu8 p < 0.01, Up3 p < 0.001), caspase 4 (Uu8 p < 0.05, 
      Up3 p < 0.01), NOD-like receptor pyrin domain-containing 3 (Uu8 p < 0.05), and 
      receptor-interacting protein kinase 3 (p < 0.05). CONCLUSIONS: By inducing 
      apoptosis in HBMEC as main constituents of the blood-brain barrier, Ureaplasma 
      spp. may provoke barrier breakdown. Simultaneous suppression of inflammatory cell 
      death may additionally attenuate host defense strategies. Ultimate consequence 
      could be invasive and long-term CNS infections by Ureaplasma spp.
FAU - Silwedel, Christine
AU  - Silwedel C
AUID- ORCID: 0000-0002-9678-326X
AD  - University Children's Hospital, University of Wuerzburg, Josef-Schneider-Str. 2, 
      97080, Wuerzburg, Germany. Silwedel_C@ukw.de.
FAU - Haarmann, Axel
AU  - Haarmann A
AD  - Department of Neurology, University of Wuerzburg, Josef-Schneider-Str. 11, 97080, 
      Wuerzburg, Germany.
FAU - Fehrholz, Markus
AU  - Fehrholz M
AD  - University Children's Hospital, University of Wuerzburg, Josef-Schneider-Str. 2, 
      97080, Wuerzburg, Germany.
FAU - Claus, Heike
AU  - Claus H
AD  - Institute for Hygiene and Microbiology, University of Wuerzburg, 
      Josef-Schneider-Str. 2, 97080, Wuerzburg, Germany.
FAU - Speer, Christian P
AU  - Speer CP
AD  - University Children's Hospital, University of Wuerzburg, Josef-Schneider-Str. 2, 
      97080, Wuerzburg, Germany.
FAU - Glaser, Kirsten
AU  - Glaser K
AD  - University Children's Hospital, University of Wuerzburg, Josef-Schneider-Str. 2, 
      97080, Wuerzburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20190214
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Oncogene Proteins v-fos)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Brain/*cytology
MH  - Caspases/classification/genetics/metabolism
MH  - Endothelial Cells/*microbiology/*physiology
MH  - Gene Expression Regulation, Bacterial/drug effects/genetics
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Microvessels/*cytology
MH  - Oncogene Proteins v-fos/genetics/metabolism
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - RNA, Messenger/metabolism
MH  - Time Factors
MH  - Ureaplasma/genetics/*pathogenicity
MH  - Ureaplasma Infections/pathology
MH  - bcl-2 Homologous Antagonist-Killer Protein/genetics/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
PMC - PMC6374915
OTO - NOTNLM
OT  - Apoptosis
OT  - Caspase
OT  - HBMEC
OT  - Meningitis
OT  - Neuroinflammation
OT  - Ureaplasma parvum
OT  - Ureaplasma urealyticum
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they 
      have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2019/02/16 06:00
MHDA- 2019/05/29 06:00
PMCR- 2019/02/14
CRDT- 2019/02/16 06:00
PHST- 2018/10/30 00:00 [received]
PHST- 2019/01/24 00:00 [accepted]
PHST- 2019/02/16 06:00 [entrez]
PHST- 2019/02/16 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2019/02/14 00:00 [pmc-release]
AID - 10.1186/s12974-019-1413-8 [pii]
AID - 1413 [pii]
AID - 10.1186/s12974-019-1413-8 [doi]
PST - epublish
SO  - J Neuroinflammation. 2019 Feb 14;16(1):38. doi: 10.1186/s12974-019-1413-8.