Induction of lipopolysaccharide-binding protein gene expression in cultured rat pulmonary artery smooth muscle cells by interleukin 1 beta.

Abstract

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.

Lipopolysaccharide Binding Protein Potentiates Airway Reactivity in a Murine Model of Allergic Asthma

“…induce LBP expression by pulmonary vascular smooth muscle cells (27) and type II epithelial cells (28). In vivo, LBP levels were previously reported to be Ͼ100-fold higher in BALF obtained from asthmatic subjects following segmental allergen challenge compared with those in normal controls (12).…”

Rna Expression in the Early Characterization of Hepatotoxicants in Wistar Rats by High–Density Dna Microarrays

“…48 The inflammatory response induced by LPS is regulated by interleukins, such as IL-1 and IL-6 binding protein that were also up-regulated. 49 Acute toxicity by CT results in liver steatosis, centrilobular necrosis, and elevated serum enzymes released from damaged hepatocytes and chronic exposures cause cirrhosis and hepatocellular carcinoma. 50,51 CT is primarily metabolized to a peroxy radical by CYP2E1, resulting in an active metabolite responsible for increased lipid peroxidation.…”

Recognition of Bacterial Endotoxin in the Lungs

“…However, when the complementary DNA (cDNA) for rat LBP was cloned, Northern blot analysis of tissues from rats with acute phase reactions revealed an increased signal in the lung and kidney RNA, although the signal was much less intense than in liver RNA (39). Subsequently, Wong and coworkers showed that rat pulmonary artery smooth-muscle cells cultured in the presence of IL-1 ␤ produced an activity similar or identical to LBP (40). This established that LBP could be produced in the lungs, particularly in the setting of acute inflammation, but the biologic importance of LBP production by vascular smooth muscle cells required further study.…”