Effect of acidosis on IL-8 and MCP-1 during hypoxia and reoxygenation in human NT2-N neurons.

Abstract

Inflammation probably plays a significant role in perinatal brain injury. To study the contribution of locally produced cytokines, the effect on cell death of addition of IL-8 and MCP-1 or antibodies to these, and the impact of acidosis, human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and reoxygenated for 21 h. After 3 h of hypoxia with neutral medium, IL-8 was significantly increased compared to controls (150 (100-250)% vs. 100 (85-115)%, p=0.023). After 21 h of neutral reoxygenation, both IL-8 (380 (110-710)% vs. 150 (85-260)%, p=0.041) and monocyte chemoattractant protein-1 (MCP-1) (650 (440-2000)% vs. 310 (230-340)%, p=0.007) were significantly increased compared to controls. After 3 h of hypoxia, both IL-8 (p=0.002) and MCP-1 (p=0.008) were significantly lower in cells with acidotic compared with cells with neutral medium. Acidosis during reoxygenation, however, significantly increased IL-8 release, whereas MCP-1 release was diminished. Similar effects of acidosis were seen in normoxic controls. The cells also secreted RANTES and IP-10, but not 8 other cytokines tested. We found no effect on cell death, measured by MTT assay, of addition of IL-8, MCP-1 or antibodies to these. We conclude that human NT2-N neurons release IL-8 and MCP-1 during 21 h of reoxygenation after 3 h of hypoxia. Acidosis led to a differential effect on IL-8 and MCP-1, with increased IL-8 and decreased MCP-1, both during reoxygenation and in normoxic controls. IL-8 and MCP-1 had no effect on cell death.

• Authors: Elisabeth Frøyland, Elena Didenko Pedersen, Anne-Katrine Kvissel, Runar Almaas, Anne Pharo, Bjørn Steen Skålhegg, Tom Eirik Mollnes, Terje Rootwelt
• Journal: Brain research (Brain Res) Vol. 1113 Issue 1 Pg. 64-73 (Oct 03 2006) ISSN: 0006-8993 [Print] Netherlands
• PMID: 16919250 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Chemokine CCL2
• Chemokine CCL5
• Interleukin-8
• Neurofilament Proteins
• Tetrazolium Salts
• Thiazoles
• neurofilament protein H
• thiazolyl blue
• Glucose
• Oxygen

Topics

• Acidosis (metabolism)
• Antibodies (pharmacology)
• Cell Hypoxia (physiology)
• Cell Line
• Chemokine CCL2 (immunology, metabolism)
• Chemokine CCL5 (metabolism)
• Dose-Response Relationship, Drug
• Fluorescent Antibody Technique (methods)
• Gene Expression Regulation (drug effects)
• Glucose (deficiency)
• Humans
• Hypoxia
• Interleukin-8 (immunology, metabolism)
• Neurofilament Proteins (metabolism)
• Neurons (physiology)
• Oxygen (administration & dosage)
• Statistics, Nonparametric
• Tetrazolium Salts
• Thiazoles
• Time Factors