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Induction of pulmonary Mn superoxide dismutase mRNA by interleukin-1
1Research Service, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, NY 12208.
Abstract:
We have previously demonstrated that intratracheal (IT) but not intraperitoneal (IP) administration of 5 micrograms tumor necrosis factor (TNF) or interleukin-1 (IL-1) selectively enhances pulmonary Mn superoxide dismutase (Mn SOD) mRNA, leading to increased Mn SOD protein and enzyme activity, and protects rats against O2 toxicity. In this study, we demonstrated that enhancement of pulmonary Mn SOD mRNA by TNF or IL-1 was highly dependent on the route of administration. IT insufflation of 5 micrograms TNF or IL-1 selectively enhanced levels of pulmonary but not splenic or renal Mn SOD mRNA. In contrast, IP or intravenous (i.v.) administration of TNF (5 micrograms) or IL-1 (5, 20, or 50 micrograms) had little or no effect on levels of Mn SOD mRNA in the lung, spleen, or kidney. Both TNF and IL-1, whether given by IT, IP, or i.v. administration, had no effect on levels of Cu, Zn SOD mRNA. IP administration of 2 mg/kg actinomycin D 2 h before IT insufflation of IL-1 paradoxically increased the level of pulmonary Mn SOD mRNA without affecting the level of Cu,Zn SOD or beta-actin mRNA in IL-1-treated rats. Nuclear runoff transcription assay revealed that IT insufflation of IL-1 enhanced the rate on MN SOD but not Cu,Zn SOD mRNA synthesis. We conclude that IL-1-induced increase in pulmonary Mn SOD mRNA is at least in part regulated at the transcriptional level.
Insights
Intratracheal administration of tumor necrosis factor (TNF) or interleukin-1 (IL-1) selectively increases pulmonary manganese superoxide dismutase (Mn SOD) mRNA. This route-dependent effect is crucial for enhancing Mn SOD levels and protecting against oxygen toxicity.
Area of Science:
- Biochemistry
- Molecular Biology
- Pulmonary Medicine
Background:
- Previous studies showed intratracheal (IT) but not intraperitoneal (IP) administration of tumor necrosis factor (TNF) or interleukin-1 (IL-1) enhances pulmonary manganese superoxide dismutase (Mn SOD) mRNA.
- This enhancement leads to increased Mn SOD protein, enzyme activity, and protection against oxygen toxicity.
Purpose of the Study:
- To investigate the route-dependency of TNF and IL-1 in enhancing pulmonary Mn SOD mRNA levels.
- To determine the effect of these cytokines on Mn SOD mRNA synthesis and regulation.
Main Methods:
- Administration of TNF or IL-1 via IT, IP, or intravenous (IV) routes in rats.
- Quantification of Mn SOD and Cu, Zn SOD mRNA levels in lung, spleen, and kidney.
- Use of actinomycin D to assess mRNA stability.
- Nuclear runoff transcription assays to evaluate mRNA synthesis rates.
Main Results:
- IT administration of TNF or IL-1 selectively increased pulmonary Mn SOD mRNA, with no effect on splenic or renal Mn SOD mRNA.
- IP or IV administration of TNF or IL-1 had minimal to no effect on Mn SOD mRNA levels in any organ.
- Neither TNF nor IL-1 affected Cu, Zn SOD mRNA levels regardless of administration route.
- IT IL-1 administration enhanced Mn SOD mRNA synthesis, indicating transcriptional regulation.
Conclusions:
- The enhancement of pulmonary Mn SOD mRNA by IL-1 is significantly dependent on the route of administration.
- IL-1-induced increases in pulmonary Mn SOD mRNA are, at least in part, regulated at the transcriptional level.