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- Andersson, P, et al.
(författare)
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Inhibition of neutrophil dependent cytotoxicity for human endothelial cells by ACE inhibitors
- 2014
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 80:5, s. 339-345
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme inhibitors (ACEi) have immunomodulating properties and have been suggested to protect against endothelial injury, for example myocardial infarction and reperfusion injury. We tested whether two ACEi (captopril and enalapril), differing in a thiol group, protected human umbilical vein endothelial cells (HUVEC) from cytotoxicity induced by polymorphonuclear neutrophils (PMN) in vitro, when cells were activated by tumour necrosis factor-α (TNFα) or the arachidonate derivative lipoxin-A4 (LXA4), using separate cytotoxicity pathways. When 51Cr labelled HUVEC were treated with captopril (0–500 μm) or enalapril (0–100 μm) for 2 h and then activated by TNFα (100 ng/ml) for 24 h, a significant, dose-dependent reduction of 51Cr release was observed. Similarly, captopril reduced 51Cr release when LXA4 (0.1 μm) was used to stimulate PMN for 4 h. Among previously defined mechanisms of significance for the cytotoxic reaction, expression of ICAM-1, but not intracellular Ca2+ changes in PMN or PMN adherence to HUVEC, were reduced by ACEi treatment. Moreover, both ACEi inhibited HUVEC surface expression of TNFα receptor I (but not II). Thus, these ACEi, particularly captopril, interfere with PMN-induced cytotoxicity for endothelial cells by modulating pro-inflammatory surface receptors, which is a novel effect that might be explored for further therapeutic approaches.
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- Cederholm, Tommy, et al.
(författare)
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Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients
- 2007
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 262:2, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We asked if single nucleotide polymorphisms (SNP) in inflammatory cytokine genes related to 3-year survival in ill elderly subjects and if genotypes differed between the elderly and a younger control population. Design. Prospective observational study. Setting. Two geriatric departments at a university hospital. Subjects. Eighty three acutely admitted geriatric patients (83 ± 7 year, 70% women) and 207 young healthy subjects (40 ± 1 year, 37% women) were included. Outcome measures. Single nucleotide polymorphisms in the genes of tumour necrosis factor (TNF)-α–308 G/A, interleukin (IL)-1β–511 C/T, IL-6–174 G/C and IL-10–1082 A/G were analysed. In the geriatric patients SNP in lymphotoxin (LT)-α +252 G/A and serum levels of TNF-α, IL-6, IL-10, soluble IL-I receptor(R)II were also determined, as well as the 3-year mortality. Results. The allele distribution did not differ significantly between the elderly and the young. In the female elderly, 3-year survival was doubled (P < 0.05) in those with the high-producing genotypes of IL-6 –174 GG and TNF-α -308 GA compared with those with low-producing alleles. In contrast, men with high-producing LT-α +252 AA and IL-1β–511 CT&TT genotypes displayed halved 3-year survival (P < 0.05) compared with those with low-producing genotypes, whereas possession of the high-producing IL-10 –1082 GG genotype favoured survival. Serum IL-10 was higher in the high-producing IL-10 genotype in females. Conclusion. As high-producing IL-6 –174 genotype favoured 3-year survival in women, whereas the likewise high-producing LT-α +252 and IL-1β -511 genotypes were associated with poor survival in men, we conclude that the specific genotypes, in association with gender, may act as determinants for survival in elderly patients.
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