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Cytokine-activated human mesangial cells generate the neutrophil chemoattractant, interleukin 8
Z Brown1, R M Strieter, S W Chensue
1Department of Renal Medicine, University College, Middlesex School of Medicine, London, United Kingdom.
Insights
Human mesangial cells stimulated by IL-1 alpha or TNF alpha produce IL-8. Dexamethasone partially inhibited IL-8 release, suggesting mesangial cells initiate glomerular inflammation via IL-8.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Glomerular inflammation involves complex cellular interactions.
- Mesangial cells (MC) are key components of the glomerulus.
- The role of MC in producing inflammatory mediators requires elucidation.
Purpose of the Study:
- To investigate the capacity of human mesangial cells to produce interleukin-8 (IL-8).
- To determine the effect of inflammatory cytokines and dexamethasone on IL-8 production by MC.
- To assess the potential role of MC-derived IL-8 in glomerular inflammatory processes.
Main Methods:
- Primary human mesangial cells were cultured in vitro.
- Cells were stimulated with interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and lipopolysaccharide (LPS).
- Interleukin-8 (IL-8) mRNA expression and protein levels (cell-associated and extracellular) were quantified. Dexamethasone treatment was also assessed.
Main Results:
- IL-1 alpha and TNF alpha, but not LPS, induced significant expression of IL-8 mRNA and protein in mesangial cells.
- Dexamethasone partially inhibited the release of extracellular IL-8.
- Cell-associated IL-8 and IL-8 mRNA levels remained largely unaffected by dexamethasone.
Conclusions:
- Human mesangial cells actively produce the chemotactic cytokine IL-8 in response to specific inflammatory stimuli.
- Dexamethasone exerts a partial inhibitory effect on extracellular IL-8 release.
- Mesangial cells likely play a direct role in initiating and propagating glomerular inflammation through IL-8 generation.
Abstract:
Human mesangial cells (MC) in culture, when stimulated by interleukin 1 alpha(IL-1 alpha) or tumour necrosis factor (TNF alpha), but not with lipopolysaccharide (LPS), express interleukin 8 (IL-8) mRNA, and both cell associated and extracellular IL-8. Dexamethasone treatment of mesangial cells induced partial inhibition of the release of extracellular IL-8, while cell-associated IL-8 and IL-8 mRNA were not significantly altered. We propose that the mesangial cell has a direct role in the initiation and propagation of inflammatory events within the glomerulus via the generation of the chemotactic cytokine IL-8.