SUMMARYThe purpose of this study was to determine if proinflammatory cytokines are up-regulated during reperfusion following sublethal ischaemia, and whether concurrent up-regulation of antioxidant enzymes occurs. Open-chest rats were subjected to 15 min of ischaemia followed by 1 or 3 h reperfusion (R). Myocardium from the ischaemic zone showed a significantly higher (P < 0 . 01) generation of thiobarbituric acid-reactive substances at 1 h and 3 h R. Northern blots showed a weak signal in controls for IL-6 mRNA (0 . 13 Ϯ 0 . 01); this was elevated to 0 . 68 Ϯ 0 . 12 at 1 h and 0 . 69 Ϯ 0 . 10 at 3 h R. Neither IL-1b nor tumour necrosis factor-alpha (TNF-a) were detectable in controls. IL-1b rose to 0 . 78 Ϯ 0 . 07 at 1 h and 0 . 51 Ϯ 0 . 08 at 3 h R, and TNF-a rose to 0 . 69 Ϯ 0 . 10 at 1 h and 0 . 38 Ϯ 0 . 15 at 3 h R. Western blotting showed no signals in the control, but readily detectable signals at 1 h R; these remained high (IL-6) or decreased (IL-1b and TNF-a) at 3 h R. mRNA analysis for antioxidant enzymes revealed a weak signal in controls for catalase (CAT; 0 . 16 Ϯ 0 . 08), glutathione peroxidase (GSH-Px; 0 . 15 Ϯ 0 . 06) and superoxide dismutase (SOD; 0 . 21 Ϯ 0 . 05). After 1 h R, levels increased significantly for CAT (0 . 46 Ϯ 0 . 10; P < 0 . 025) and GSH-Px (0 . 51 Ϯ 0 . 13; P < 0 . 01), but remained similar to controls for SOD (0 . 26 Ϯ 0 . 15). At 3 h R the mRNA levels were significantly elevated for the three enzymes (CAT 0 . 48 Ϯ 0 . 13; GSH-Px 0 . 47 Ϯ 0 . 10; SOD 0 . 54 Ϯ 0 . 08). We conclude that mRNA for proinflammatory cytokines is expressed early in reperfusion, and that the proteins are present in heart tissue. Also, reperfusion is associated with rapid expression of genes for antioxidant enzymes, which may enhance reactive oxygen intermediate (ROI) scavenging.
Numerous factors contribute to host resistance to infection with Schistosoma mansoni. Although several studies have investigated the eosinophil as an effector cell of protective responses, its true role remains unclear. In vitro, human, but not mouse, eosinophils can kill schistosomula. Studies on schistosome infection susceptibility in naive or vaccinated eosinophil-deficient mice have yielded conflicting results. Using the gamma-irradiated cercariae (irr-cerc) model, we vaccinated interleukin (IL)-5 transgenic mice in parallel with background-matched controls (C3H/HeN) to examine whether innate eosinophilia contributes to increased protection from a challenge infection. In our laboratory, mean peripheral blood eosinophil (PBE) levels in IL-5 transgenic mice were 21,000 mm3, whereas in naive C3H/HeN mice this value was 240 mm3. In 3 separate experiments, both groups of vaccinated mice showed significant resistance to challenge infection. However, there was no significant difference in the percent worm reduction between transgenic IL-5 C3H mice (mean % protection = 44.3; range = 42-45%) and the control C3H/HeN mice (mean % protection = 51.7; range = 41-64%). Our findings indicate that high levels of innate PBE due to constitutive production of IL-5 do not augment irr-cerc-stimulated immunity.
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