Gene interactions and pathways from curated databases and text-mining
Cardiovasc Res 2003, PMID: 14553834

8-isoprostane increases expression of interleukin-8 in human macrophages through activation of mitogen-activated protein kinases.

Scholz, Hanne; Yndestad, Arne; Damås, Jan Kristian; Waehre, Torgun; Tonstad, Serena; Aukrust, Pål; Halvorsen, Bente

OBJECTIVE

8-isoprostane is a marker of oxidative stress in vivo and increased plasma and urine levels are found in patients with vascular disease and in atherosclerotic plaques. Inflammatory chemokines such as interleukin (IL)-8 seem to play an important pathogenic role in atherogenesis. We therefore investigated the effects of 8-isoprostane on the expression of inflammatory chemokines with consciousness on IL-8 (mRNA and protein) in human macrophages. In addition, we studied the involvement of mitogen-activated protein kinases (ERK 1/2 and p38 MAPK) and nuclear factor-kappaB (NF-kappaB) in this process.

RESULTS

8-isoprostane (10 microM) induced IL-8 expression (mRNA and protein), measured by real-time quantitative RT-PCR and enzyme immunoassay, respectively, in both THP-1 macrophages and human monocyte-derived macrophages. Moreover, 8-isoprostane increased mRNA expression of macrophage inflammatory protein-1alpha as determined by RNase protection assay. In this process, 8-isoprostane induced the activation of two major MAP-kinases; ERK 1/2 and p38 MAPK. Furthermore, the ERK 1/2 inhibitor, PD98059, and the p38 MAPK inhibitor, SB203580, markedly reduced 8-isoprostane-induced IL-8 expression (mRNA and protein), while inhibition of NF-kappaB activation and translocation had no significant effect on IL-8 expression.

CONCLUSIONS

We show that 8-isoprostane increases IL-8 expression in human macrophages involving both ERK 1/2 and p38 MAPK, but not NF-kappaB signaling pathway. These findings further support a link between oxidative stress/lipid peroxidation and inflammation in human macrophages and suggest a role for 8-isoprostane in this process. This 8-isoprostane-induced chemokine expression might be involved in the pathogenesis of atherosclerosis as well as other inflammatory disorders.

Diseases/Pathways annotated by Medline MESH: Inflammation, MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

IL-8 ⊣ NF-kappaB: " Furthermore, the ERK 1/2 inhibitor, PD98059, and the p38 MAPK inhibitor, SB203580, markedly reduced 8-isoprostane induced IL-8 expression ( mRNA and protein ), while inhibition of NF-kappaB activation and translocation had no significant effect on IL-8 expression "

IL-8 → p38: " Furthermore, the ERK 1/2 inhibitor, PD98059, and the p38 MAPK inhibitor, SB203580, markedly reduced 8-isoprostane induced IL-8 expression ( mRNA and protein ), while inhibition of NF-kappaB activation and translocation had no significant effect on IL-8 expression "

IL-8 → MAPK: " Furthermore, the ERK 1/2 inhibitor, PD98059, and the p38 MAPK inhibitor, SB203580, markedly reduced 8-isoprostane induced IL-8 expression ( mRNA and protein ), while inhibition of NF-kappaB activation and translocation had no significant effect on IL-8 expression "

IL-8 → MAPK: " We show that 8-isoprostane increases IL-8 expression in human macrophages involving both ERK 1/2 and p38 MAPK , but not NF-kappaB signaling pathway "

IL-8 → ERK 1/2: " We show that 8-isoprostane increases IL-8 expression in human macrophages involving both ERK 1/2 and p38 MAPK, but not NF-kappaB signaling pathway "

IL-8 → ERK 1/2: " We show that 8-isoprostane increases IL-8 expression in human macrophages involving both ERK 1/2 and p38 MAPK, but not NF-kappaB signaling pathway "

Manually curated Databases

No curated data.