We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFa production induced by Gram-positive and Gram-negative bacteria.
- Authors
Temple, S E L; Cheong, K Y; Almeida, C M; Price, P; Waterer, G W
- Abstract
Improved understanding of how host genetic variation affects resistance to microbial pathogens could lead to better treatment and/or prevention of infectious diseases. The lymphotoxin alpha (LTA)+250 and CD14-159 polymorphisms are associated with differences in susceptibility or outcome to several infections. We stimulated peripheral blood mononuclear cells (PBMC) from 22 healthy individuals with purified lipopolysaccharide (LPS), heat-killed Escherichia coli or Streptococcus pneumoniae. TNFα intracellular protein levels were measured by flow cytometry and mRNA was quantitated by RT-PCR. TNFα mRNA levels were higher in LTA+250GG subjects after 4 h incubation with LPS compared with LTA+250AA (T test, P=0.001). In contrast, after 8 h incubation with S. pneumoniae, there was slightly more TNFα mRNA in cells from LTA+250AA subjects. After 4 h incubation with LPS or E. coli, CD14-159TT subjects had higher TNFα mRNA levels than CD14-159CC (P=0.05, 0.033, respectively). Neither polymorphism affected the proportion of cells expressing intracellular TNFα protein. This suggests that the polymorphisms affected transcription and that other regulatory mechanisms affect production of TNFα protein. The effect of these two polymorphisms on TNFα mRNA production is stimulus dependent, with opposite effects observed for Gram-positive and Gram-negative stimuli.
- Subjects
PATHOGENIC microorganisms; COMMUNICABLE diseases; GENETIC research
- Publication
Genes & Immunity, 2003, Vol 4, Issue 4, p283
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/sj.gene.6363963