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Interleukin-1 and glomerular mesangial cells
C Zoja1, A Rambaldi, G Remuzzi
1Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Insights
Interleukin-1 (IL-1) stimulates its own gene expression in human mesangial cells. This autocrine regulation, mediated by IL-1 receptor type I, is crucial for inflammatory processes in the glomerulus.
Area of Science:
- Immunology
- Cell Biology
- Renal Physiology
Background:
- Interleukin-1 (IL-1) is known to stimulate various gene expressions in human mesangial cells.
- The autocrine regulation of IL-1 by mesangial cells remained to be elucidated.
Purpose of the Study:
- To investigate whether IL-1 regulates its own gene expression in human mesangial cells.
- To determine the role of IL-1 receptor type I in this process.
Main Methods:
- Human mesangial cells were treated with varying concentrations of IL-1.
- Northern blot analysis was used to assess IL-1 mRNA expression.
- Recombinant IL-1 receptor antagonist was employed to block IL-1 signaling.
Main Results:
- IL-1 dose-dependently induced IL-1 mRNA expression in mesangial cells.
- IL-1 receptor type I, constitutively expressed on mesangial cells, mediated this effect.
- Recombinant IL-1 receptor antagonist inhibited IL-1-induced IL-1 mRNA, IL-6, and IL-8 gene expression.
Conclusions:
- IL-1 exhibits autocrine regulation of its own gene expression in human mesangial cells.
- This IL-1 autocrine loop, involving IL-1 receptor type I, plays a significant role in glomerular inflammatory responses.
Abstract:
Our previous in vitro study demonstrated that interleukin-1 (IL-1) stimulates gene expression and production of leukocyte chemotactic factors, colony-stimulating factors and interleukin-6 in human mesangial cells in culture. Here we investigated whether IL-1 regulates its own gene expression in human mesangial cells. Northern blot experiments showed that IL-1 induced IL-1 mRNA expression in a dose-dependent manner. The action of IL-1 on mesangial cells was mediated through the IL-1 receptor type I, which is constitutively expressed by mesangial cells. Recombinant IL-1 receptor antagonist blocked the IL-1 mRNA as well as interleukin-6 and interleukin-8 gene expression induced by IL-1. These data support the crucial role played by IL-1 in regulating mesangial cell cytokine genes within the glomerulus during immunological or inflammatory processes.
