INDUCTION OF LIPOPOLYSACCHARIDE-BINDING PROTEIN GENE-EXPRESSION IN CULTURED RAT PULMONARY-ARTERY SMOOTH-MUSCLE CELLS BY INTERLEUKIN-1-BETA

Lipopolysaccharide (LPS)-binding protein (LBP) binds with high affinit y to LPS, and the LBP-LPS complex enhances cellular inflammatory respo nses to LPS. Although it is present in normal serum, LBP is also induc ed as part of the acute phase response. Synthesis of LBP is thought to be limited to the liver, but we have recently reported significant ex trahepatic (including pulmonary) LBP mRNA expression in in vivo rat mo dels of sepsis and inflammation. In the present study, we tested the h ypothesis that a cellular source of pulmonary LBP in the rat may be va scular smooth muscle, by exposing cultured rat pulmonary artery smooth muscle cells (RPASMC) to cytokines and LPS. Treatment of RPASMC for 4 and 24 h with a combination of tumor necrosis factor alpha, interleuk in 1 beta (IL-1 beta), interferon gamma, and LPS resulted in significa nt LBP mRNA expression. Of this mixture, IL-1 beta alone was sufficien t to induce LBP mRNA expression in both a time- and dose-dependent man ner. The effects of IL-beta on LBP mRNA expression were significantly antagonized by IL-1 receptor antagonist protein. Furthermore, supernat ants from RPASMC treated with IL-1 beta enhanced the binding of [I-125 ]ASD-LPS by the macrophage cell line RAW 264.7, indicative of LBP bioa ctivity. We conclude that pulmonary artery smooth muscle cells stimula ted with IL-1 beta produce a transcript for LBP or a homologous produc t in vitro. Local production of LBP could play an important role in th e pulmonary response to inflammation and sepsis.