| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of California, Davis, CA, USA; Department of Internal Medicine-1, and Department of Microbiology, Kumamoto University School of Medicine, Kumamoto, Japan
2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of California, Davis, CA, USA
3 Department of Pathology, University of Vermont, Burlington, VT, USA
4 Department of Internal Medicine-1, and Department of Microbiology, Kumamoto University School of Medicine, Kumamoto, Japan
* To whom correspondence should be addressed. E-mail: avanderv{at}zoo.uvm.edu.
Acute lung inflammation and injury was induced by intranasal instillation of lipopolysaccaride (LPS) in normal and NOS2-deficient (NOS2-/-) C57BL/6 mice. LPS-induced increases in extravasated airway neutrophils, and in lung lavage fluid levels of tumor necrosis factor-
(TNF-) and macrophage inflammatory protein-2 (MIP-2), were markedly lower in NOS2-/- mice compared to wild-type mice, indicating that NOS2-derived nitric oxide (NO.) participates in inflammatory cytokine production and neutrophil recruitment. Instillation of LPS also caused increased total lung lavage protein levels and induction of matrix metalloproteinase-9 (MMP-9) and mucin (MUC) 5AC, as indices of lung epithelial injury and/or mucus hyperplasia, and increased tyrosine nitration of lung lavage proteins, a marker of oxidative injury. All these responses were less pronounced in NOS2-/- mice compared to wild-type mice. Inhibition of NOS activity also suppressed production of TNF- and MIP-2 by LPS-stimulated mouse alveolar MH-S macrophages, and this was restored by NO.-donors, illustrating involvement of NO. in macrophage cytokine signaling. Oligonucleotide microarray (GeneChip®) analysis of global lung gene expression revealed that LPS inhalation induced a range of transcripts encoding pro-inflammatory cytokines and chemokines, stress-inducible factors and other extracellular factors, and suppressed mRNAs encoding certain cytoskeletal proteins and signaling proteins, responses that were generally attenuated in NOS2-/- mice. Comparison of both mouse strains revealed altered expression of several cytoskeletal proteins, cell surface proteins, and signaling proteins in NOS2-/- mice, changes that may partly explain the reduced responsiveness to LPS. Collectively, our results suggest that NOS2 participates in the acute inflammatory response to LPS by multiple mechanisms, by involvement in pro-inflammatory cytokine signaling and by altering the expression of various genes that affect inflammatory-immune responses to LPS.
This article has been cited by other articles:
|
|
 |
|
  H. E. Marshall, E. N. Potts, Z. T. Kelleher, J. S. Stamler, W. M. Foster, and R. L. Auten Protection from Lipopolysaccharide-induced Lung Injury by Augmentation of Airway S-Nitrosothiols Am. J. Respir. Crit. Care Med., July 1, 2009; 180(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Takemoto, K. Ogino, M. Shibamori, T. Gondo, Y. Hitomi, T. Takigawa, D.-H. Wang, J. Takaki, H. Ichimura, Y. Fujikura, et al. Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1419 - L1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Helyes, K. Elekes, J. Nemeth, G. Pozsgai, K. Sandor, L. Kereskai, R. Borzsei, E. Pinter, A. Szabo, and J. Szolcsanyi Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1173 - L1181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Farley, L. F. Wang, H. M. Razavi, C. Law, M. Rohan, D. G. McCormack, and S. Mehta Effects of macrophage inducible nitric oxide synthase in murine septic lung injury Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1164 - L1172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Werber, I. Shalit, I. Fabian, G. Steuer, T. Weiss, and H. Blau Moxifloxacin inhibits cytokine-induced MAP kinase and NF-{kappa}B activation as well as nitric oxide synthesis in a human respiratory epithelial cell line J. Antimicrob. Chemother., March 1, 2005; 55(3): 293 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jeyaseelan, H. W. Chu, S. K. Young, and G. S. Worthen Transcriptional Profiling of Lipopolysaccharide-Induced Acute Lung Injury Infect. Immun., December 1, 2004; 72(12): 7247 - 7256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. McCluskie, M. A. Birrell, S. Wong, and M. G. Belvisi Nitric Oxide as a Noninvasive Biomarker of Lipopolysaccharide-Induced Airway Inflammation: Possible Role in Lung Neutrophilia J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 625 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ma, X. Cui, S. Wang, J. Zhang, E. V. Nishanian, W. Wang, R. A. Wesley, and R. L. Danner Nitric oxide post-transcriptionally up-regulates LPS-induced IL-8 expression through p38 MAPK activation J. Leukoc. Biol., July 1, 2004; 76(1): 278 - 287. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
