Tumor necrosis factor-alpha (TNF-£\) 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-£\ 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-£eB DNA binding activity; and expression of IL-1£], 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-1£], and iNOS as compared with WT mice. On the contrary, significant increase of NF-£eB 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-£\ decreases P. aeruginosa-induced mortality in burned mice is through a negative regulation of TLR4 and iNOS.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0902108-125407 |
| Date | 02 September 2008 |
| Creators | Chen, Pei-hsuan |
| Contributors | Lee-wei Cheng, Ming-hong Tai, Ching-mei Hsu, Li-chung Hsu |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0902108-125407 |
| Rights | off_campus_withheld, Copyright information available at source archive |
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