Tumor necrosis factor superfamily ligand mRNA expression profiles differ between humans and mice during homeostasis and between various murine kidney injuries.

BACKGROUND: Several tumour necrosis factor (TNF) based therapeutics have already been approved for human use and several others are emerging. Therefore, we determined the mRNA expression levels of the TNF superfamily ligands (TNFSF) - e.g. TNF-α, lymphotoxin (LT)-α, LT-ß, Fas-L (CD95-L), TNF-related apoptosis-inducing ligand (TRAIL), TNF-related weak inducer of apoptosis (TWEAK), 4-1BBL, OX40-L (CD252) and amyloid precursor protein (APP) in healthy human and mouse solid organs. METHODS: We used quantitative real time-PCR to analyse mRNA expression levels of TNFSF ligands. Murine models of acute ischemic renal injury, chronic oxalate nephropathy, and immune complex glomerulonephritis were used. Renal injury was assessed by PAS staining, and infiltrating immune cells were analysed by immunohistochemistry. Data was analysed using non-parametric ANOVA (non-parametric; Kruskal-Wallis test). RESULTS: We observed significant differences in the mRNA expression levels of TNFSF ligands in human and mouse solid organs. Furthermore, we determined their mRNA expressions during acute and chronic kidney injuries in mice. Our data demonstrate that the mRNA expression levels of TNFSF vary depending on the type of tissue injury - for example, acute ischemic renal injury, chronic crystalline nephropathy, and immune complex glomerulonephritis. In addition, we observed that mRNA expressions of TNFSF ligands are differentially regulated during the course of a transient ischemic renal injury (IRI) and chronic kidney modelling. We observed that TNF-α, LT-ß, and 4-1BBL were significantly upregulated during the progression of IRI and crystal-induced chronic kidney disease (CKD), whereas only 4-1BBL and TNF-α were significantly upregulated and LT-ß was significantly downregulated during the progression of immune complex glomerulonephritis. The mRNA expression of Fas-L was higher during IRI whereas it decreased in a time dependent manner during the progression of crystal-induced CKD. CONCLUSION: We conclude that the injury- and species-specific differences of TNFSF ligands must be considered in order to avoid the misinterpretation and wrong conclusions during data extrapolation between species.

The expressive level and clinical significance of tumor necrosis factor ligands related molecule 1A in peripheral blood of patients with viral myocarditis / 中国医师进修杂志

Objective To explore the expressive level and clinical significance of tumor necrosis factor ligands related molecule 1A (TL1A) in peripheral blood of patients with viral myocarditis.Methods In 70 patients with viral myocarditis (viral myocarditis group) and 70 normal controls (control group),the plasma level of TL1A was detected by enzyme linked immunosorbent assay and the mRNA level of TL1A was detected by real-time quantitative reverse transcription polymerase chain reaction.Results The plasma level of TL1A in viral myocarditis group was significantly higher than that in control group [(1.37 ± 0.41) μg/L vs.(0.85 ± 0.22) μg/L](P=0.000).The level of peripheral blood TL1A mRNA in viral myocarditis group was significantly higher than that in control group (0.39 ±0.17 vs.0.31 ±0.11,P =0.001).Conclusion The level of TL1A in patients with viral myocarditis is increased,and TL1A may participate in the occurrence of viral myocarditis.