PMID- 22053092
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20220317
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 86
IP  - 2
DP  - 2012 Feb
TI  - Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate 
      immune system are essential for the response to lipopolysaccharide by epithelial 
      and stromal cells of the bovine endometrium.
PG  - 51
LID - 10.1095/biolreprod.111.092718 [doi]
AB  - Infection of the bovine endometrium with Gram-negative bacteria commonly causes 
      uterine disease. Toll-like receptor 4 (TLR4) on cells of the immune system bind 
      Gram-negative bacterial lipopolysaccharide (LPS), stimulating the secretion of 
      the proinflammatory cytokines interleukin 1B (IL1B) and IL6, and the chemokine 
      IL8. Because the endometrium is the first barrier to infection of the uterus, the 
      signaling cascade triggered by LPS and the subsequent expression of inflammatory 
      mediators were investigated in endometrial epithelial and stromal cells, and the 
      key pathways identified using short interfering RNA (siRNA) and biochemical 
      inhibitors. Treatment of endometrial cells with ultrapure LPS stimulated an 
      inflammatory response characterized by increased IL1B, IL6, and IL8 mRNA 
      expression, and IL6 protein accumulation in epithelial cells, and by increased 
      IL1B and IL8 mRNA expression, and IL6 and IL8 protein accumulation in stromal 
      cells. Treatment of endometrial cells with LPS also induced the degradation of 
      IKB and the nuclear translocation of NFKB, as well as rapid phosphorylation of 
      mitogen-activated protein kinase 3/1 (MAPK3/1) and MAPK14. Knockdown of TLR4 or 
      its signaling adaptor molecule, myeloid differentiation factor 88 (MYD88), using 
      siRNA reduced the inflammatory response to LPS in epithelial and stromal cells. 
      Biochemical inhibition of MAPK3/1, but not JNK or MAPK14, reduced LPS-induced 
      IL1B, IL6, and IL8 expression in endometrial cells. In conclusion, epithelial and 
      stromal cells have an intrinsic role in innate immune surveillance in the 
      endometrium, and in the case of LPS this recognition occurs via TLR4- and 
      MYD88-dependent cell signaling pathways.
FAU - Cronin, James G
AU  - Cronin JG
AD  - Institute of Life Science, School of Medicine, Swansea University, United 
      Kingdom. j.cronin@swansea.ac.uk
FAU - Turner, Matthew L
AU  - Turner ML
FAU - Goetze, Leopold
AU  - Goetze L
FAU - Bryant, Clare E
AU  - Bryant CE
FAU - Sheldon, I Martin
AU  - Sheldon IM
LA  - eng
GR  - BB/D02028X/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - F005121/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/F005121/2/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/F017596/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/F005121/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120229
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cells, Cultured
MH  - Endometrium/cytology/*drug effects/metabolism
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Immunity, Innate/*physiology
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 14/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Myeloid Differentiation Factor 88/drug effects/genetics/*physiology
MH  - NF-kappa B/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Signal Transduction/*physiology
MH  - Stromal Cells/*drug effects/metabolism
MH  - Toll-Like Receptor 4/drug effects/genetics/*physiology
PMC - PMC4396703
MID - EMS49353
OID - NLM: EMS49353
EDAT- 2011/11/05 06:00
MHDA- 2012/07/10 06:00
PMCR- 2015/04/14
CRDT- 2011/11/05 06:00
PHST- 2011/11/05 06:00 [entrez]
PHST- 2011/11/05 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
PHST- 2015/04/14 00:00 [pmc-release]
AID - biolreprod.111.092718 [pii]
AID - 10.1095/biolreprod.111.092718 [doi]
PST - epublish
SO  - Biol Reprod. 2012 Feb 29;86(2):51. doi: 10.1095/biolreprod.111.092718. Print 2012 
      Feb.