DIVERGENT EFFECTS OF LPS ON EXPRESSION OF IL-1 RECEPTOR FAMILY MEMBRANES IN MONONUCLEAR PHAGOCYTES IN-VITRO AND IN-VIVO

Three molecules, interleukin ` (IL-1) receptor I(IL-1RI), IL-1 recepto r II (IL-1RII or decoy) and IL-1 receptor accessory protein (IL-1R AcP or IL-1RIII), are involved in IL-1 binding and signal transduction. I n addition, three homologous genes (T1/ST2, MyD88 and rsc786) have bee n identified. Expression of the signal transducing type I R and of the decoy type II R in human monocytes is regulated by pro- and anti-infl ammatory signals. The present study was designed to evaluate comprehen sively how a prototypic pro-inflammatory signal, bacterial lipopolysac charide (LPS), affects expression of IL-1R family members in mononucle ar phagocytes in vitro and in vivo. Resting human monocytes expressed high levels of IL-1RII, IL-1R AcP, MyD88 and rsc786, whereas low level s of IL-1RI and T1/ST2 were present. In vitro exposure to LPS augmente d expression of IL-1RI, T1/ST2 and MyD88, whereas it inhibited that of IL-1RII and rsc786. Expression of IL-1R AcP in monocytes was less sub stantially affected by LPS. The expression of IL1R family members was also studied in organs of mice given LPS. As expected on the basis of in vitro results, organs (e.g. spleen, lungs and peritoneal exudate ce lls) from LPS-treated mice showed increased levels of IL-1RI, T1/ST2 a nd MyD88. Intriguingly, while expression of IL-1RII was inhibited in p eritoneal macrophages after LPS, in accordance with in vitro results, increased IL-1RII mRNA was observed in organs such as liver, lungs and spleen. This unexpected effect of LPS was drastically reduced in mice rendered neutropenic by 5-fluorouracil. Therefore, we conclude that t he apparent induction of IL-1RII in certain organs of LPS-treated mice is due to recruitment of myeloid cells which express high levels of d ecoy RII. Therefore, members of IL-1R family are independently and div ergently regulated in mononuclear phagocytes exposed to the prototypic pro-inflammatory signal LPS in vitro and in vivo. (C) 1998 Academic P ress.