This Article Full Text Full Text (PDF) All Versions of this Article: 2003-0263OCv1 30/2/228    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raychaudhuri, B. Articles by Thomassen, M. J. Search for Related Content PubMed PubMed Citation Articles by Raychaudhuri, B. Articles by Thomassen, M. J.

Surfactant Blocks Lipopolysaccharide Signaling by Inhibiting both Mitogen-Activated Protein and IB Kinases in Human Alveolar Macrophages

Department of Pulmonary and Critical Care Medicine, Department of Cancer Biology, and Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio

Address correspondence to: Dr. Mary Jane Thomassen, Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A90, Cleveland, OH 44195. E-mail: thomasm{at}ccf.org

Surfactant plays an important role in lung homeostasis and is also involved in maintaining innate immunity within the lung. Lipopolysaccharide (LPS) from gram-negative bacteria is known to elicit acute proinflammatory responses in lung diseases such as acute respiratory distress syndrome and pneumonia, among others. Our previous studies demonstrated that the clinically used, natural surfactant product Survanta inhibited proinflammatory cytokine secretion from LPS-stimulated human alveolar macrophages. Here we investigated the effect of Survanta on mitogen-activated protein (MAP) and IB kinases. Survanta blocked LPS-induced activation of nuclear factor-B, a key regulatory transcription factor involved in cytokine production, by preventing phosphorylation of IB, and its subsequent degradation. IB is phosphorylated by specific kinases (IKK) before degradation. Survanta inhibited activity of both and ß subunits of IKK, thereby delaying the phosphorylation of IB. Interestingly, IKK- is predominant in alveolar macrophages, whereas IKK-ß predominates in monocytes. Survanta also inhibited extracellular signal–regulated kinase and p38 MAP kinase activity induced by LPS. Data are the first to show that surfactant may regulate lung homeostasis in part by inhibiting proinflammatory cytokine production through reduction of IKK and MAP kinase activity.

Abbreviations: enzyme-linked immunosorbent assay, ELISA • lipopolysaccharide, LPS • mitogen-activated protein, MAP • MAP kinase, MAPK • macrophage inflammatory protein-1, MIP-1 • nuclear factor-B, NF-B • tumor necrosis factor, TNF • whole cell extract, WCE

This article has been cited by other articles:

				Y. Sumita, T. Sugiura, Y. Kawaguchi, S. Baba, M. Soejima, Y. Murakawa, M. Hara, and N. Kamatani Genetic polymorphisms in the surfactant proteins in systemic sclerosis in Japanese: T/T genotype at 1580 C/T (Thr131Ile) in the SP-B gene reduces the risk of interstitial lung disease Rheumatology, March 1, 2008; 47(3): 289 - 291. [Abstract] [Full Text] [PDF]

				M. Ikegami, E. A. Scoville, S. Grant, T. Korfhagen, W. Brondyk, R. K. Scheule, and J. A. Whitsett Surfactant Protein-D and Surfactant Inhibit Endotoxin-Induced Pulmonary Inflammation Chest, November 1, 2007; 132(5): 1447 - 1454. [Abstract] [Full Text] [PDF]