PMID- 16476493
OWN - NLM
STAT- MEDLINE
DCOM- 20060629
LR  - 20171116
IS  - 0165-2427 (Print)
IS  - 0165-2427 (Linking)
VI  - 111
IP  - 3-4
DP  - 2006 Jun 15
TI  - Genotyping of Toll-like receptor 4, myeloid differentiation factor 2 and CD-14 in 
      the horse: an investigation into the influence of genetic polymorphisms on the 
      LPS induced TNF-alpha response in equine whole blood.
PG  - 165-73
AB  - The inter- and intra-species differences in the response to lipopolysaccharides 
      (LPS) are well recognised in mammalian species. It has been hypothesized that 
      these differences can be attributed to genetic polymorphisms in the components 
      involved in LPS signal transduction. These components include the cluster of 
      differentiation factor 14 (CD-14), a membrane bound protein on the surface of 
      mononuclear cells that recognises LPS and a receptor complex consisting of 
      Toll-like receptor-4 (TLR-4) and myeloid differentiation factor-2 (MD-2). 
      Sequencing of these three proteins in humans and mice revealed that all three are 
      susceptible to polymorphic alterations, influencing the response to LPS. Previous 
      experiments in the horse showed large inter-individual variations in the response 
      to LPS. With the aim to assess this inter-individual variation, we performed a 
      whole blood assay in 10 healthy horses as a functional assay to study the 
      responsiveness to LPS. In 3 out of the 10 horses, LPS-induced TNF-alpha 
      production was significantly lower compared to the overall mean. Subsequently the 
      entire cDNA sequence encoding for the TLR-4, MD-2 and CD-14 protein was 
      documented for each horse. Although mutations were observed in the sequence of 
      TLR-4, these could not be related to an altered response to LPS in the 
      concentration used in this study, as determined in the whole blood assay. Despite 
      the various mutations found in the TLR-4 receptor protein, no alterations could 
      be found in either the MD-2 or CD-14 gene, which are obviously more conserved 
      structures.
FAU - Werners, A H
AU  - Werners AH
AD  - Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of 
      Veterinary Medicine, Utrecht University, Yalelaan 16, 3584 CM, Utrecht, The 
      Netherlands. a.h.werners@vet.uu.nl
FAU - Bull, S
AU  - Bull S
FAU - Vendrig, J C
AU  - Vendrig JC
FAU - Smyth, T
AU  - Smyth T
FAU - Bosch, R R
AU  - Bosch RR
FAU - Fink-Gremmels, J
AU  - Fink-Gremmels J
FAU - Bryant, C E
AU  - Bryant CE
LA  - eng
PT  - Journal Article
DEP - 20060214
PL  - Netherlands
TA  - Vet Immunol Immunopathol
JT  - Veterinary immunology and immunopathology
JID - 8002006
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Lymphocyte Antigen 96)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Animals
MH  - Cytotoxicity Tests, Immunologic/veterinary
MH  - Female
MH  - Horses/blood/*genetics/*immunology
MH  - Lipopolysaccharide Receptors/*genetics/immunology
MH  - Lipopolysaccharides/immunology/*pharmacology
MH  - Lymphocyte Antigen 96/*genetics/immunology
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - RNA/chemistry/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction/veterinary
MH  - Sequence Analysis, DNA
MH  - Toll-Like Receptor 4/*genetics/immunology
MH  - Tumor Necrosis Factor-alpha/*immunology
EDAT- 2006/02/16 09:00
MHDA- 2006/06/30 09:00
CRDT- 2006/02/16 09:00
PHST- 2005/05/03 00:00 [received]
PHST- 2005/11/29 00:00 [revised]
PHST- 2005/12/22 00:00 [accepted]
PHST- 2006/02/16 09:00 [pubmed]
PHST- 2006/06/30 09:00 [medline]
PHST- 2006/02/16 09:00 [entrez]
AID - S0165-2427(06)00003-1 [pii]
AID - 10.1016/j.vetimm.2005.12.003 [doi]
PST - ppublish
SO  - Vet Immunol Immunopathol. 2006 Jun 15;111(3-4):165-73. doi: 
      10.1016/j.vetimm.2005.12.003. Epub 2006 Feb 14.