Interleukin-10 expression is autoregulated at the transcriptional level in human and murine kupffer cells
✍ Scribed by Percy A. Knolle; Anja Uhrig; Ulrike Protzer; Martin Trippler; Rainer Duchmann; Karl-Hermann Meyer zum Büschenfelde; Guido Gerken
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 172 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Interleukin 10 (IL-10) is known to downregulate immune responses. The regulation of IL-10 gene expression therefore determines the outcome of local immune reactions. We investigated time course and downregulation of IL-10 production in primary Kupffer's cells (KC), which are known to secrete IL-10 in response to endotoxin challenge. Human and murine KC were isolated by centrifugal elutriation and investigated for IL-10 gene expression by a two-step amplification procedure (reverse transcriptasepolymerase chain reaction [PCR] followed by T7-polymerase chain reaction). We show that IL-10 messenger ribonucleic acid (mRNA) showed a G450 fold increase in KC 2 hours after endotoxin challenge. IL-10 protein release from KC strictly depended on de novo protein synthesis. Endotoxin mediated increase in IL-10 gene expression was downregulated by exogenous (G350-fold reduction of IL-10 mRNA level), as well as endogenous IL-10 protein, showing a negative autoregulatory feedback loop. IL-10 receptor expression was found to be constitutive and functional in KC. Early expression of IL-10 in KC may be of functional relevance to the outcome of immune and inflammatory reactions in the liver sinusoid. The negative autoregulation of IL-10 expression may represent a mechanism to regain a state of functional responsiveness in the microenvironment towards new proinflammatory stimuli. In conclusion, autoregulatory downregulation of IL-10 expression in KC may account for important regulatory steps of local immune response in the liver sinusoid. (HEPATOLOGY 1998;27:93-99.