Mesangial cell-derived interleukin-10 modulates mesangial cell response to lipopolysaccharide
| Autor: | B, Fouqueray, V, Boutard, C, Philippe, A, Kornreich, A, Marchant, J, Perez, M, Goldman, L, Baud |
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| Rok vydání: | 1995 |
| Předmět: |
Lipopolysaccharides
Male Mice Inbred BALB C Mice Inbred C3H Base Sequence Dose-Response Relationship Drug Molecular Sequence Data Nitric Oxide Polymerase Chain Reaction Recombinant Proteins Glomerular Mesangium Interleukin-10 Mice Transforming Growth Factor beta Escherichia coli Animals Cytokines RNA Messenger Cells Cultured DNA Primers Research Article |
| Zdroj: | The American journal of pathology. 147(1) |
| ISSN: | 0002-9440 |
| Popis: | Interleukin (IL)-10 is a novel cytokine produced by a variety of cells, including monocytes/macrophages, upon exposure to lipopolysaccharide (LPS). Recent observations indicate that, in turn, IL-10 exerts suppressive effects on macrophage response to LPS. Because mesangial cells are also a target for LPS, we have examined the potential role of IL-10 in the regulation of mesangial cell response to LPS. To this aim, we have studied the synthesis and the autocrine/paracrine function of IL-10 in cultured mouse mesangial cells. IL-10 mRNA expression and IL-10 protein secretion were determined by a reverse transcription polymerase chain reaction technique and a specific enzyme-linked immunosorbent assay, respectively. No IL-10 mRNA expression was detectable in unactivated cells. LPS induced IL-10 mRNA expression in a dose-dependent fashion (1 to 100 micrograms/ml). In addition, LPS induced IL-10 protein release that was both dose dependent (1 to 100 micrograms/ml) and time dependent (24 to 72 hours). We have also studied the effect of IL-10 on the production of inflammatory mediators by LPS-activated mouse mesangial cells. Whereas recombinant IL-10 inhibited the generation of tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta by 90 and 60%, respectively, it did not affect the formation of nitric oxide-derived nitrite (NO2-) and nitrate (NO3-). As shown by the use of anti-IL-10 monoclonal antibody, endogenously produced IL-10 affected the generation of TNF-alpha but neither that of IL-1 beta nor that of NO2- and NO3-. Finally, we have examined whether conditions known to also reduce the generation of TNF-alpha modified the expression of IL-10. Of all the conditions tested, only the addition of desferrioxamine and transforming growth factor-beta were found to increase IL-10 release. Together, these data demonstrate that mesangial cell-derived IL-10 has important regulatory effects on the inflammatory response of these cells to LPS because of its capacity to blunt TNF-alpha generation. |
| Databáze: | OpenAIRE |
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