Early Increase in Alveolar Macrophage Prostaglandin 15d-PGJ2 Precedes Neutrophil Recruitment into Lungs of Cytokine-Insu
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Early Increase in Alveolar Macrophage Prostaglandin 15d-PGJ2 Precedes Neutrophil Recruitment into Lungs of Cytokine-Insufflated Rats Ana Fernandez-Bustamante,1,3,6 Jelena Klawitter,1,4 Paul Wilson,3 Nancy D. Elkins,3 Amanda Agazio,1,3 Takahiro Shibata,5 Koji Uchida,5 Uwe Christians,1,4 and John E. Repine2,3
ABSTRACT—Early detection and prevention is an important goal in acute respiratory distress syndrome research. We determined the concentration of the anti-inflammatory 15-deoxy-Δ12,14prostaglandin-J2 (15d-PGJ2) and other components of the cyclopentenone prostaglandin cascade in relation to lung inflammation in cytokine (IL-1/LPS)-insufflated rats. We found that 15d-PGJ2 levels increase in the bronchoalveolar lavage (BAL) fluid of rats insufflated with cytokines 2 h before. BAL 15d-PGJ2 increases preceded neutrophil recruitment, lung injury, and oxidative stress in the lungs of cytokine-insufflated rats. 15d-PGJ2 was localized in alveolar macrophages that decreased following cytokine insufflation. 15d-PGJ2 may constitute an early biomarker of lung inflammation and may reflect an endogenous attempt to regulate ongoing inflammation in macrophages and elsewhere after cytokine insufflation. KEY WORDS: 15d-PGJ2; anti-inflammatory prostaglandin; cyclopentenone prostaglandins; lung macrophages; inflammation; ARDS.
INTRODUCTION The acute respiratory distress syndrome (ARDS) is a rapidly progressing highly fatal disorder characterized by lung inflammation and oxidative stress [1–3]. Using the new Berlin definition [4], the diagnosis of ARDS is usually made relatively late in the development of ARDS when there are frank clinical abnormalities. Waiting until ARDS Ana Fernandez-Bustamante and Jelena Klawitter contributed equally to this manuscript. 1
Department of Anesthesiology, University of Colorado SOM, AO-1, MS 8202, 12631 E 17th Ave., Aurora, CO 80045, USA 2 Department of Medicine, University of Colorado SOM, Aurora, CO, USA 3 Webb Waring Center, University of Colorado SOM, Aurora, CO, USA 4 iC42 Integrated Solutions in Systems Biology, University of Colorado SOM, Aurora, CO, USA 5 Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan 6 To whom correspondence should be addressed at Webb Waring Center, University of Colorado SOM, Aurora, CO, USA. E-mail: [email protected]
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2013 Springer Science+Business Media New York
is established, however, has made it extremely difficult to treat, and accordingly, no specific treatments exist for ARDS. Recently, the ARDS research focus is switching to learning more about the early lung inflammatory processes and potential adaptive defensive responses that might occur before the development of symptomatic ARDS [5]. The goal of this new research is to discover ways to make an earlier diagnosis and then institute preventive rather than treatment interventions in order to change the clinical course and outcome of ARDS before it becomes established and extremely difficult to treat. 15-Deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2) is a
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