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Published on: May 31, 2018
Soluble immune complexes stimulate production of interleukin-1 by cultured rat glomerular mesangial cells
1Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Insights
Immune complexes (IC) stimulate mesangial cells (MC) to produce Interleukin-1 (IL-1), a key inflammatory mediator. This finding suggests IC may worsen kidney inflammation by increasing IL-1 production.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Interleukin-1 (IL-1) is a potent inflammatory mediator involved in numerous immune responses.
- IL-1 has been detected in inflamed kidney glomeruli, suggesting a role in renal inflammatory conditions.
- Mesangial cells (MC) are crucial components of the glomerulus and can be influenced by various stimuli.
Purpose of the Study:
- To investigate whether immune complexes (IC) can induce Interleukin-1 (IL-1) production by mesangial cells (MC).
- To explore the role of IC as regulators of IL-1 production in the context of kidney inflammation.
Main Methods:
- Isolated rat glomerular mesangial cells (MC) were incubated with soluble immune complexes (IC) derived from rat glomerular basement membrane.
- Interleukin-1 (IL-1) production was quantified using the mouse thymocyte assay.
- Indomethacin was used to block prostaglandin effects, and IL-1 activity was reassessed.
- Neutralization of biological activity with a specific anti-IL-1 antibody confirmed the findings.
Main Results:
- Soluble IC significantly induced the production of IL-1 by cultured mesangial cells (MC).
- Addition of indomethacin led to a further increase in IL-1 production, suggesting a complex regulatory interaction.
- The observed biological activity was specifically attributed to IL-1, as confirmed by antibody neutralization.
Conclusions:
- Immune complexes (IC) are potent stimulators of Interleukin-1 (IL-1) production in mesangial cells (MC).
- IC-induced IL-1 production may contribute to augmented local inflammatory responses within the kidney.
- These findings highlight a potential mechanism by which IC exacerbate kidney inflammation.
Abstract:
Interleukin-1 (IL-1) is a pleiotropic factor, eliciting a broad set of immunologic and inflammatory events. We have previously shown that IL-1 is present in inflamed glomeruli. To evaluate factors that might regulate of IL-1 production, we tested the effects of substances accessible to mesangial cells (MC): immune complexes (IC) are known to modulate MC function. We have attempted to assess the ability of soluble IC derived from rat glomerular basement membrane to induce the production of IL-1. When isolated MC were incubated with the soluble IC, substantial amount of IL-1 could be detected in the supernatants as measured by the mouse thymocyte assay. To block the effect of prostaglandins on the IL-1 assay, we cultured the MC with the addition of indomethacin and assayed IL-1 activity in the culture supernatants. The use of indomethacin resulted in a further increase in IL-1 production. These biological activities were neutralized by a specific antibody to IL-1. In the present report, we show that IC represent important sources of stimulation of MC for the production of IL-1. We speculate that IC could augment local inflammatory responses in the kidney partly due to their capacity to induce the production of IL-1.
