Interleukin-10 expression is autoregulated at the transcriptional level in human and murine kupffer cells

Percy A. Knolle, Anja Uhrig, Ulrike Protzer, Martin Trippler, Rainer Duchmann, Karl-Hermann Meyer zum Büschenfelde, Guido Gerken
1998 Hepatology  
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
more » ... olymerase 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.)
doi:10.1002/hep.510270116 pmid:9425923 fatcat:bjd6kswi7ng5livxetedic7gbe