Regulation of manganese superoxide dismutase: IL-1 and TNF induction in pulmonary artery and microvascular endothelial cells

doi:10.1016/0006-291X(92)92406-N

Biochemical and Biophysical Research Communications

Volume 188, Issue 1, 15 October 1992, Pages 453-462

https://doi.org/10.1016/0006-291X(92)92406-N Get rights and content

Abstract

IL-1 and TNF are important mediators in the inflammatory response, and have been associated with endothelial cell damage in the lung. TNF and IL-1 cell-mediated injury has been proposed to occur through an increase in intracellular oxygen free radical production. However, these cytokines have also been shown to protect the lung from hyperoxia-mediated oxidant injury. In this paper we evaluated the response of the antioxidant enzymes, MnSOD and Cu/ZnSOD to IL-1, TNF, and LPS in both rat pulmonary artery and microvascular endothelial cells. These mediators produced an increase in MnSOD but not Cu/ZnSOD expression in both rat pulmonary endothelial cells. An additive effect was observed with co-treatment by the cytokines with LPS. The MnSOD mRNA induction is dependent upon a transcriptional event, but did not require $de novo$ protein synthesis.

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In the present study, the effect of manganese (Mn) on antioxidant status and the expression of the manganese superoxide dismutase (MnSOD) gene in cultured primary myocardial cells collected from the chick embryos was investigated. The hypothesis that Mn supplementation would enhance the expression of MnSOD in cultured primary myocardial cells of chick embryos was tested. Eggs collected from Mn-depleted Arbor Acres laying breeder hens were incubated for 10 days and then myocardial cells were isolated and cultivated for 8 days. The embryonic myocardial cells on day 6 were treated with Mn in the cell culture medium at different time points when the proportion of cells showing spontaneous contraction was over 95% after the 3-day primary culture. A completely randomized design involving a 3 Mn levels (0, 0.5 and 1.0 mmol L⁻¹)×3 incubation time points (12, 24 and 48 h) factorial arrangement of treatments (n=6) was used in the current experiment. The results showed that MnSOD activity and mRNA expression level were induced by Mn and increased with incubation time, which supported the hypothesis that Mn would enhance the expression of the MnSOD gene, and thus might protect myocardial cells from oxidative stress during the chick embryonic development.
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Citation Excerpt :
IL-1β is one of the major pro-inflammatory cytokines that is involved in the pathogenesis of vascular dysfunction. It has been reported that IL-1β not only enhances the generation of superoxide anions in arteries [22,23] that can scavenge NO and reduce the bioavailability of endothelium-derived NO [24] but also decreases eNOS protein expression in endothelial cells [25] and thereby contributes to the impairment of endothelium-dependent relaxation [26]. The IL-1β/IR-1R1 signalling axis leads to the activation of NF-κB and the transcription of other pro-inflammatory factors and thus establishes a self-amplifying cytokine network.
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Regulation of manganese superoxide dismutase: IL-1 and TNF induction in pulmonary artery and microvascular endothelial cells

Abstract

Biochem. Biophys. Res. Comm

J. Biol. Chem

Cell. Immunol

J. Appl. Physiol

J. Clin. Invest

Science

Am. J. Pathol

FASEB J

Cancer Res

Kidney Int

FASEB J

J. Appl. Physiol

Am. J. Physiol

J. Tissue Cult. Methods

J. Tissue Cult. Methods