PMID- 24635133
OWN - NLM
STAT- MEDLINE
DCOM- 20141201
LR  - 20140416
IS  - 1600-0897 (Electronic)
IS  - 1046-7408 (Linking)
VI  - 71
IP  - 5
DP  - 2014 May
TI  - The TLR2 ligand FSL-1 and the TLR5 ligand Flagellin mediate pro-inflammatory and 
      pro-labour response via MyD88/TRAF6/NF-kappaB-dependent signalling.
PG  - 401-17
LID - 10.1111/aji.12229 [doi]
AB  - PROBLEM: Toll-like receptors (TLRs) 2 and 5 induce inflammation via the adapter 
      proteins myeloid differentiation factor 88 (MyD88) and TNFR-associated factor 6 
      (TRAF6) and the transcription factor nuclear factor-kappa B (NF-kappaB). The aims of 
      this study were to determine the effects of the TLR5 ligand flagellin and the 
      TLR2 ligand FSL-1 on pro-inflammatory and pro-labour mediators in human fetal 
      membranes and myometrium, and to establish whether their actions are dependent on 
      MyD88, TRAF6 and NF-kappaB. METHOD OF STUDY: Tissue explants were performed to 
      determine the effect of flagellin and FSL-1 on pro-labour mediators in fetal 
      membranes and myometrium. siRNA knockdown was performed in primary amnion and 
      myometrium cells to determine the role of MyD88, TRAF6 and NF-kappaB. RESULTS: 
      Flagellin and FSL-1 increased pro-inflammatory cytokines (IL-6 and IL-8), MMP-9 
      expression and activity, and COX-2 expression and prostaglandin release. siRNA 
      knockdown of TLR2 decreased FSL-1 induced production of IL-6, IL-8, COX-2, 
      prostaglandins and MMP-9; similarly, siRNA knockdown of TLR5 decreased flagellin 
      induced production of these pro-labour mediators. The effects of flagellin and 
      FSL-1 are mediated by MyD88 and TRAF6, as siRNA knockdown of MyD88 and TRAF6 
      decreased flagellin and FSL-1 induced pro-labour mediators. Additionally, the 
      effects of flagellin and FSL-1 are mediated via NF-kappaB, as flagellin and FSL-1 
      increased NF-kappaB transcriptional activity, and the NF-kappaB inhibitor BAY 11-7082 
      attenuated flagellin and FSL-1 induced expression and secretion of pro-labour 
      mediators. CONCLUSION: TLR2 engagement by the synthetic lipoprotein FSL-1 and 
      TLR5 engagement by bacterial flagellin enhances pro-inflammatory and pro-labour 
      mediators in human fetal membranes and myometrium via MyD88/TRAF6/NF-kappaB.
CI  - (c) 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Lim, Ratana
AU  - Lim R
AD  - Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and 
      Gynaecology, University of Melbourne, Heidelberg, Vic., Australia; Mercy 
      Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Vic, Australia.
FAU - Barker, Gillian
AU  - Barker G
FAU - Lappas, Martha
AU  - Lappas M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140317
PL  - Denmark
TA  - Am J Reprod Immunol
JT  - American journal of reproductive immunology (New York, N.Y. : 1989)
JID - 8912860
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (Diglycerides)
RN  - 0 (FSL-1 lipoprotein, synthetic)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitriles)
RN  - 0 (Oligopeptides)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Sulfones)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR5 protein, human)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 5)
RN  - 12777-81-0 (Flagellin)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 3.4.24.35 (MMP9 protein, human)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Cyclooxygenase 2
MH  - Diglycerides/*pharmacology
MH  - Extraembryonic Membranes/drug effects/metabolism
MH  - Female
MH  - Fetus
MH  - Flagellin/*pharmacology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Interleukin-6/genetics/metabolism
MH  - Interleukin-8/genetics/metabolism
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Myeloid Differentiation Factor 88/*genetics/metabolism
MH  - Myometrium/drug effects/metabolism
MH  - NF-kappa B/*genetics/metabolism
MH  - Nitriles/pharmacology
MH  - Oligopeptides/*pharmacology
MH  - Pregnancy
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - Sulfones/pharmacology
MH  - TNF Receptor-Associated Factor 6/*genetics/metabolism
MH  - Tissue Culture Techniques
MH  - Toll-Like Receptor 2/antagonists & inhibitors/*genetics/metabolism
MH  - Toll-Like Receptor 5/antagonists & inhibitors/*genetics/metabolism
OTO - NOTNLM
OT  - Foetal membranes
OT  - MyD88
OT  - NFkappa B
OT  - TLR2
OT  - TLR5
OT  - myometrium
EDAT- 2014/03/19 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/03/19 06:00
PHST- 2013/12/05 00:00 [received]
PHST- 2014/02/17 00:00 [accepted]
PHST- 2014/03/19 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1111/aji.12229 [doi]
PST - ppublish
SO  - Am J Reprod Immunol. 2014 May;71(5):401-17. doi: 10.1111/aji.12229. Epub 2014 Mar 
      17.