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Lipopolysaccharide induces monocyte chemoattractant protein production by rat mesangial cells
J P Grande1, M L Jones, C L Swenson
1Department of Laboratory Medicine and Pathology, Mayo Graduate School of Medicine, Rochester, MN.
Abstract:
Lipopolysaccharide, a potent pro-inflammatory constituent of bacterial cell walls, is capable of promoting glomerular inflammation, by both activating circulating inflammatory cells and local interactions with renal parenchymal cells. We sought to determine whether lipopolysaccharide was capable of promoting glomerular inflammation by directly stimulating mesangial cell production of monocyte chemoattractant protein 1, a recently described cytokine capable of eliciting recruitment of mononuclear phagocytes into inflammatory foci. Northern hybridization analysis revealed dose and time-dependent induction of mRNA coding for monocyte chemoattractant protein 1 in quiescent rat mesangial cells treated with lipopolysaccharide. Lipopolysaccharide-elicited induction of monocyte chemoattractant protein mRNA was detectable after 1 hour and persisted for at least 30 hours. Media isolated from rat mesangial cell cultures stimulated by lipopolysaccharide possessed monocyte chemotactic activity that was detectable at 8 hours and peaked at 24 hours; an antimonocyte chemoattractant protein antibody blocked 87% of this chemotactic activity. We suggest that lipopolysaccharide, released from bacterial cell walls, promotes glomerular inflammation by stimulating mesangial cell production of monocyte chemoattractant protein 1.
Insights
Lipopolysaccharide (LPS) from bacterial cell walls can cause kidney inflammation. This study shows LPS directly stimulates mesangial cells to produce monocyte chemoattractant protein 1, a key inflammatory mediator.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Lipopolysaccharide (LPS) is a pro-inflammatory molecule found in bacterial cell walls.
- LPS can induce glomerular inflammation through various mechanisms.
- Monocyte chemoattractant protein 1 (MCP-1) is a cytokine that recruits mononuclear phagocytes.
Purpose of the Study:
- To investigate if LPS directly stimulates mesangial cells to produce MCP-1.
- To understand the role of LPS-induced MCP-1 in glomerular inflammation.
Main Methods:
- Northern hybridization analysis was used to detect mRNA levels.
- Rat mesangial cells were treated with LPS.
- Monocyte chemotactic activity in cell culture media was assessed.
- The effect of anti-MCP-1 antibody on chemotactic activity was evaluated.
Main Results:
- LPS induced a dose- and time-dependent increase in MCP-1 mRNA in mesangial cells.
- MCP-1 mRNA induction was observed within 1 hour and lasted over 30 hours.
- LPS-stimulated mesangial cell media exhibited significant monocyte chemotactic activity, which was largely blocked by anti-MCP-1 antibody.
Conclusions:
- Lipopolysaccharide directly stimulates rat mesangial cells to produce monocyte chemoattractant protein 1.
- This LPS-induced MCP-1 production contributes to glomerular inflammation by recruiting monocytes.
- Targeting MCP-1 may be a therapeutic strategy for LPS-induced kidney inflammation.