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 affinity to LPS, and the LBP-LPS complex enhances cellular inflammatory responses to LPS. Although it is present in normal serum, LBP is also induced as part of the acute phase response. Synthesis of LBP is though to be limited to the liver, but we have recently reported significant extrahepatic (including pulmonary) LBP mRNA expression in in vivo rat models of sepsis and inflammation. In the present study, we tested the hypothesis that a cellular source of pulmonary LBP in the rat may be vascular 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, interleukin 1 beta (IL-1 beta), interferon gamma, and LPS resulted in significant LBP mRNA expression. Of this mixture, IL-1 beta alone was sufficient to induce LBP mRNA expression in both a time- and dose-dependent manner. The effects of IL-beta on LBP mRNA expression were significantly antagonized by IL-1 receptor antagonist protein. Furthermore, supernatants from RPASMC treated with IL-1 beta enhanced the binding of [125I]ASD-LPS by the macrophage cell line RAW 264.7, indicative of LBP bioactivity. We conclude that pulmonary artery smooth muscle cells stimulated with IL-1 beta produce a transcript for LBP or a homologous product in vitro. Local production of LBP could play an important role in the pulmonary response to inflammation and sepsis.
Wong
H R
HR
Department of Anesthesiology, University of Pittsburgh School of Medicine, USA.
Pitt
B R
BR
Su
G L
GL
Rossignol
D P
DP
Steve
A R
AR
Billiar
T R
TR
Wang
S C
SC
D000209:Acute-Phase Proteins; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D015870:Gene Expression; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D000099231:Lipopolysaccharide-Binding Protein