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Hepatic inducible nitric oxide synthase expression increases upon exposure to hypergravity.

Kim HS, Jung YY, Do SI - Braz. J. Med. Biol. Res. (2014)

Bottom Line: At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules.The majority of positively stained cells showed a strong intensity of iNOS expression.These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

ABSTRACT
Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

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Effect of hypergravity exposure on pro-inflammatory cytokine production inthe livers of mice. ELISA was performed to measure the hepatic levels ofcytokines. Data are reported as the means±SE of 3 independent experiments ineach group. A, IL-1β. B, IL-6.C, IFN-γ. D, TNF-α. IL: interleukin;IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α. The centrifuged miceexhibited no significant changes in the concentrations of the 4 cytokinescompared to those of the control mice (Studentt-test).
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f03: Effect of hypergravity exposure on pro-inflammatory cytokine production inthe livers of mice. ELISA was performed to measure the hepatic levels ofcytokines. Data are reported as the means±SE of 3 independent experiments ineach group. A, IL-1β. B, IL-6.C, IFN-γ. D, TNF-α. IL: interleukin;IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α. The centrifuged miceexhibited no significant changes in the concentrations of the 4 cytokinescompared to those of the control mice (Studentt-test).

Mentions: IL-1β, IL-6, IFN-γ, and TNF-α proteins in the livers of mice exposed to hypergravitywere determined by ELISA. Figure 3 reports theconcentrations of the cytokines, normalized to controls. There were no significanteffects of hypergravity exposure on the hepatic expression levels of IL-1β (Figure 3A), IL-6 (Figure 3B), IFN-γ (Figure 3C), orTNF-α (Figure 3D). Increases in IL-1β and IL-6levels observed at 0-1 and 12-18 h after centrifugation did not reach statisticalsignificance. Although the TNF-α level rose immediately after centrifugation andpeaked at 3 h (a 1.3-fold increase compared to control), there was no significantdifference between the time points.


Hepatic inducible nitric oxide synthase expression increases upon exposure to hypergravity.

Kim HS, Jung YY, Do SI - Braz. J. Med. Biol. Res. (2014)

Effect of hypergravity exposure on pro-inflammatory cytokine production inthe livers of mice. ELISA was performed to measure the hepatic levels ofcytokines. Data are reported as the means±SE of 3 independent experiments ineach group. A, IL-1β. B, IL-6.C, IFN-γ. D, TNF-α. IL: interleukin;IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α. The centrifuged miceexhibited no significant changes in the concentrations of the 4 cytokinescompared to those of the control mice (Studentt-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230283&req=5

f03: Effect of hypergravity exposure on pro-inflammatory cytokine production inthe livers of mice. ELISA was performed to measure the hepatic levels ofcytokines. Data are reported as the means±SE of 3 independent experiments ineach group. A, IL-1β. B, IL-6.C, IFN-γ. D, TNF-α. IL: interleukin;IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α. The centrifuged miceexhibited no significant changes in the concentrations of the 4 cytokinescompared to those of the control mice (Studentt-test).
Mentions: IL-1β, IL-6, IFN-γ, and TNF-α proteins in the livers of mice exposed to hypergravitywere determined by ELISA. Figure 3 reports theconcentrations of the cytokines, normalized to controls. There were no significanteffects of hypergravity exposure on the hepatic expression levels of IL-1β (Figure 3A), IL-6 (Figure 3B), IFN-γ (Figure 3C), orTNF-α (Figure 3D). Increases in IL-1β and IL-6levels observed at 0-1 and 12-18 h after centrifugation did not reach statisticalsignificance. Although the TNF-α level rose immediately after centrifugation andpeaked at 3 h (a 1.3-fold increase compared to control), there was no significantdifference between the time points.

Bottom Line: At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules.The majority of positively stained cells showed a strong intensity of iNOS expression.These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

ABSTRACT
Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

Show MeSH
Related in: MedlinePlus