Hepatic induction of cholesterol biosynthesis ... - The FASEB Journal

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Hans P. Deigner,¶ David P. Enot,¶ Emeka I. Igwe,¶ Lucien Frappart,#. Michael Kiehntopf ... Paton, J. C., Maus, U. A., Bauer, M. Hepatic induction of cholesterol ...
The FASEB Journal • Research Communication

Hepatic induction of cholesterol biosynthesis reflects a remote adaptive response to pneumococcal pneumonia Martina Weber,* Sandro Lambeck,† Nadine Ding,㥋 Stefanie Henken,㥋 Matthias Kohl,* Hans P. Deigner,¶ David P. Enot,¶ Emeka I. Igwe,¶ Lucien Frappart,# Michael Kiehntopf,‡ Ralf A. Claus,*,† Thomas Kamradt,§ Debra Weih,** Yoram Vodovotz,††,‡‡ David E. Briles,§§ Abiodun D. Ogunniyi,㥋㥋 James C. Paton,㥋㥋 Ulrich A. Maus,㥋,1 and Michael Bauer*,†,1,2 *Department of Anaesthesiology and Intensive Care Therapy, †Center for Sepsis Control and Care, ‡Institute for Clinical Chemistry and Laboratory Medicine, and §Institute of Immunology, Jena University Hospital, Jena, Germany; 㛳Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany; ¶Biocrates Life Sciences AG, Innsbruck; Austria; # Department of Pathology, University Claude Bernard Lyon I and Inserm U590, Lyon, France; **Leibniz Institute for Age Research, Fritz-Lipmann Institute, Jena, Germany;††Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;‡‡Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania, USA;§§Department of Microbiology, University of Alabama at Birmingham, Alabama, USA;㛳㛳Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia Community-acquired pneumonia presents a spectrum of clinical phenotypes, from lobar pneumonia to septic shock, while mechanisms underlying progression are incompletely understood. In a transcriptomic and metabolomic study across tissues, we examined serotype-specific regulation of signaling and metabolic pathways in C57BL/6 mice intratracheally instilled with either serotype 19F Streptococcus pneumoniae (S19; causing lobar pneumonia), or serotype 2 S. pneumoniae (S2; causing septic pneumococcal disease,) or vehicle (Todd-Hewitt broth). Samples of lung, liver, and blood were collected at 6 and 24 h postinfection and subjected to microarray analysis and mass spectrometry. Results comprise a preferential induction of cholesterol biosynthesis in lobar pneumonia at lowinfection doses (105 colony forming units/mouse) leading to increased plasma cholesterol (vehicle: 1.8ⴞ0.12 mM, S2: 2.3ⴞ0.10 mM, S19: 2.9ⴞ0.15 mM; P