Induction of hepatic acute phase reactants by conditioned medium from lipopolysaccharide treated human dermal fibroblasts / 第二军医大学学报

ABSTRACT

To test the hypothesis that dermal fibroblasts (DF) are an important source of cytokines which elicit major changes in hepatic synthesis of acute phase reactants(APRs). Metkods Condi-tioned medium(CM) from human DF challenged with bacterial lipopolysaccharide (I,PS) was collected andIL-10 and IL-6 levels were measured- The ability of DF conditioned medium(fLPS) and dexamethasone(Dex) to mediate an hepatic acute phase response was tested on rat hepatoma H4 cells- Various concentra-tions and combinations of CM (?LPS), recombinant IL-6 (rhIL-6) and Dex were tested for their abilitiesto stimulate albumin, Q,-acid glycoprotein (AGP), a,-antitrypsin (AT) and transferrin mRNA synthesis.Results: LPS stimulated IL-6 production by DF and Dex inhibited this producti0n. IL-6 and CM+LPS in-hibited the production of albumin mRNA,while the expression of AT and AGP 0ccurred 0nly with CM+LPS+Dex. However,IL-6 alone had an inhibitory effect 0n albumin and transferrin mRNA producti0n.Dex maximized the effects 0f lL-6 and CM, and was essential f0r AGP gene expression. C0nclusion (l)LPS-treated human DF can secrete IL-6, but not IL-101 (2)DF may als0 pr0duce other cyt0kines whichmodulate hepatic pr0tein synthesis during the acute phase response l (3) Dex inhibits IL-6 production byDF, but enhances its ability to stimulate the acute phase response.