Resolution of Toll-like receptor 4-mediated acute lung injury is linked to eicosanoids and suppressor of cytokine signaling 3

被引:30
作者
Hilberath, Jan N. [2 ,3 ]
Carlo, Troy
Pfeffer, Michael A.
Croze, Roxanne H.
Hastrup, Frantz
Levy, Bruce D. [1 ]
机构
[1] Brigham & Womens Hosp, Harvard Inst Med, Div Pulm & Crit Care Med, Dept Internal Med, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA USA
基金
美国国家卫生研究院;
关键词
inflammation; lung elastance; vascular permeability; lipid mediators; macrophages; INFLAMMATION; MACROPHAGES; MICE; IDENTIFICATION; ASPIRATION; RESPONSES; PROTEINS; DELIVERY; PATHWAY; STRESS;
D O I
10.1096/fj.10-169896
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The purpose of this study was to investigate roles for Toll-like receptor 4 (TLR4) in host responses to sterile tissue injury. Hydrochloric acid was instilled into the left mainstem bronchus of TLR4-defective (both C3H/HeJ and congenic C. C3-Tlr4(Lps-d)/J) and control mice to initiate mild, self-limited acute lung injury (ALI). Outcome measures included respiratory mechanics, barrier integrity, leukocyte accumulation, and levels of select soluble mediators. TLR4-defective mice were more resistant to ALI, with significantly decreased perturbations in lung elastance and resistance, resulting in faster resolution of these parameters [resolution interval (R-i); similar to 6 vs. 12 h]. Vascular permeability changes and oxidative stress were also decreased in injured HeJ mice. These TLR4-defective mice paradoxically displayed increased lung neutrophils [(HeJ) 24 x 10(3) vs. (control) 13 x 10(3) cells/bronchoalveolar lavage]. Proresolving mechanisms for TLR4-defective animals included decreased eicosanoid biosynthesis, including cysteinyl leukotrienes (80% mean decrease) that mediated CysLT1 receptor-dependent vascular permeability changes; and induction of lung suppressor of cytokine signaling 3 (SOCS3) expression that decreased TLR4-driven oxidative stress. Together, these findings indicate pivotal roles for TLR4 in promoting sterile ALI and suggest downstream provocative roles for cysteinyl leukotrienes and protective roles for SOCS3 in the intensity and duration of host responses to ALI.-Hilberath, J N., Carlo, T., Pfeffer, M. A., Croze, R. H., Hastrup, F., Levy, B. D. Resolution of Toll-like receptor 4-mediated acute lung injury is linked to eicosanoids and suppressor of cytokine signaling 3. FASEB J. 25, 1827-1835 (2011). www.fasebj.org
引用
收藏
页码:1827 / 1835
页数:9
相关论文
共 47 条
[1]   Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[2]   Lipoxin A4 regulates bronchial epithelial cell responses to acid injury [J].
Bonnans, C ;
Fukunaga, K ;
Levy, MA ;
Levy, BD .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 168 (04) :1064-1072
[3]   Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP [J].
Bystrom, Jonas ;
Evans, Ian ;
Newson, Justine ;
Stables, Melanie ;
Toor, Iqbal ;
van Rooijen, Nico ;
Crawford, Mark ;
Colville-Nash, Paul ;
Farrow, Stuart ;
Gilroy, Derek W. .
BLOOD, 2008, 112 (10) :4117-4127
[4]   Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS [J].
Carpenter, CT ;
Price, PV ;
Christman, BW .
CHEST, 1998, 114 (06) :1653-1659
[5]   TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events [J].
Cavassani, Karen A. ;
Ishii, Makoto ;
Wen, Haitao ;
Schaller, Matthew A. ;
Lincoln, Pamela M. ;
Lukacs, Nicholas W. ;
Hogaboam, Cory M. ;
Kunkel, Steven L. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (11) :2609-2621
[6]   The lipoxin receptor ALX:: Potent ligand-specific and stereoselective actions in vivo [J].
Chiang, Nan ;
Serhan, Charles N. ;
Dahlen, Sven-Erik ;
Drazen, Jeffrey M. ;
Hay, Douglas W. P. ;
Rovati, G. Enrico ;
Shimizu, Takao ;
Yokomizo, Takehiko ;
Brink, Charles .
PHARMACOLOGICAL REVIEWS, 2006, 58 (03) :463-487
[7]   A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice [J].
Eckle, Tobias ;
Grenz, Almut ;
Laucher, Stefanie ;
Eltzschig, Holger K. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (10) :3301-3315
[8]  
Fang M, 2005, CELL MOL IMMUNOL, V2, P373
[9]   Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury [J].
Frank, James A. ;
Wray, Charlie M. ;
McAuley, Danny F. ;
Schwendener, Reto ;
Matthay, Michael A. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2006, 291 (06) :L1191-L1198
[10]   Apoptotic cells, through transforming growth factor-β, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages [J].
Freire-de-Lima, Celio G. ;
Xiao, Yi Qun ;
Gardai, Shyra J. ;
Bratton, Donna L. ;
Schiemann, William P. ;
Henson, Peter M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (50) :38376-38384