Title page for etd-0902108-125407


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URN etd-0902108-125407
Author Pei-hsuan Chen
Author's Email Address No Public.
Statistics This thesis had been viewed 5564 times. Download 1092 times.
Department Biological Sciences
Year 2007
Semester 2
Degree Master
Type of Document
Language English
Title Lack of TNF-α Receptor 1 Decreases Pseudomonas aeruginosa-induced Mortality in Burned Mice through Negative Regulation of Toll-like Receptor 4
Date of Defense 2008-06-20
Page Count 49
Keyword
  • iNOS
  • TLR4
  • Abstract Tumor necrosis factor-alpha (TNF-α) is a potent proinflammatory cytokine, inducing the acute-phase response that leads to physiological changes that serve to eliminate the infecting organisms. Toll-like receptors (TLRs) comprise a family of pattern-recognition receptors that detect conserved molecular products of microorganisms. To evaluate the role of TNF-α and TLRs in Pseudomonas aeruginosa infection-induced mortality in thermal injured mice, the wild type (WT), Tnfrsf1a-/-, and TLR4-/- mice were injected the P. aeruginosa in the back at 8 hr after 30% total body surface area burn. At 24 hr after burn, lung tissues of mice were harvested for assays of wet/dry ratio; microvascular dysfunction, myeloperoxidase (MPO) activity, NF-κB DNA binding activity; and expression of IL-1β, iNOS, p-JNK, and TLR4. Injection of P. aeruginosa after burn induced a survival rate in Tnfrsf1a-/- 60% TBSA burn=100%, WT 60% TBSA burn=10%, WT 30% TBSA burn +P.A = 60%, Tnfrsf1a-/- 30% TBSA burn+p.A. = 30%. respectively. The high mortality in Tnfrsf1a-/- mice is related to a significant increase of pulmonary microvascular dysfunction; neutrophil infiltration, bacterial counts of blood and lung; and expression of TLR4, IL-1β, and iNOS as compared with WT mice. On the contrary, significant increase of NF-κB DNA binding activity of lung was observed only in WT mice. When iNOS inhibitor SMT was given immediately after burn to WT and Tnfrsf1a-/- mice, the P. aeruginosa induced increases of pulmonary edema, pulmonary permeability, and lung bacterial counts were decreased significantly in Tnfrsf1a-/- mice, suggesting that TNF-α decreases P. aeruginosa-induced mortality in burned mice is through a negative regulation of TLR4 and iNOS.
    Advisory Committee
  • Ming-hong Tai - chair
  • Li-chung Hsu - co-chair
  • Ching-mei Hsu - advisor
  • Lee-wei Cheng - advisor
  • Files
  • etd-0902108-125407.pdf
  • indicate in-campus access immediately and off_campus access in a year
    Date of Submission 2008-09-02

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