| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Activity Determine the Severity of Endotoxin-Induced Acute Lung Injury1
,
,,
* Department of Cell and Developmental Biology,
Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine,
Department of Cancer Biology, Vanderbilt University School of Medicine, and
Department of Veterans Affairs, Nashville, TN 37232;
¶ Section of Pulmonary, Critical Care, and Sleep Medicine, University of Illinois, Chicago, IL 60612; and
|| Department of Immunology, Inflammation, and Pulmonary Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543
Activation of innate immunity in the lungs can lead to a self-limited inflammatory response or progress to severe lung injury. We investigated whether specific parameters of NF-
B pathway activation determine the outcome of acute lung inflammation using a novel line of transgenic reporter mice. Following a single i.p. injection of Escherichia coli LPS, transient NF-B activation was identified in a variety of lung cell types, and neutrophilic inflammation resolved without substantial tissue injury. However, administration of LPS over 24 h by osmotic pump (LPS pump) implanted into the peritoneum resulted in sustained, widespread NF-B activation and neutrophilic inflammation that culminated in lung injury at 48 h. To determine whether intervention in the NF-B pathway could prevent progression to lung injury in the LPS pump model, we administered a specific IB kinase inhibitor (BMS-345541) to down-regulate NF-B activation following the onset of inflammation. Treatment with BMS-345541 beginning at 20 h after osmotic pump implantation reduced lung NF-B activation, concentration of KC and MIP-2 in lung lavage, neutrophil influx, and lung edema measured at 48 h. Therefore, sustained NF-B activation correlates with severity of lung injury, and interdiction in the NF-B pathway is beneficial even after the onset of lung inflammation.
This article has been cited by other articles:
|
|
 |
|
  L. T. Krug, C. M. Collins, L. M. Gargano, and S. H. Speck NF-{kappa}B p50 Plays Distinct Roles in the Establishment and Control of Murine Gammaherpesvirus 68 Latency J. Virol., May 15, 2009; 83(10): 4732 - 4748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Bastarache and T. S. Blackwell Development of animal models for the acute respiratory distress syndrome Dis. Model. Mech., May 1, 2009; 2(5-6): 218 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Han, M. Joo, M. B. Everhart, J. W. Christman, F. E. Yull, and T. S. Blackwell Myeloid cells control termination of lung inflammation through the NF-{kappa}B pathway Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L320 - L327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Jin, Y. Lho, L. Connelly, Y. Wang, X. Yu, L. Saint Jean, T. C. Case, K. Ellwood-Yen, C. L. Sawyers, N. A. Bhowmick, et al. The Nuclear Factor-{kappa}B Pathway Controls the Progression of Prostate Cancer to Androgen-Independent Growth Cancer Res., August 15, 2008; 68(16): 6762 - 6769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. T. Stathopoulos, T. P. Sherrill, D.-S. Cheng, R. M. Scoggins, W. Han, V. V. Polosukhin, L. Connelly, F. E. Yull, B. Fingleton, and T. S. Blackwell Epithelial NF-{kappa}B activation promotes urethane-induced lung carcinogenesis PNAS, November 20, 2007; 104(47): 18514 - 18519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Stathopoulos, A. Kollintza, C. Moschos, I. Psallidas, T. P. Sherrill, E. N. Pitsinos, S. Vassiliou, M. Karatza, S. A. Papiris, D. Graf, et al. Tumor Necrosis Factor-{alpha} Promotes Malignant Pleural Effusion Cancer Res., October 15, 2007; 67(20): 9825 - 9834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Joo, M. Kwon, R. T. Sadikot, P. J. Kingsley, L. J. Marnett, T. S. Blackwell, R. S. Peebles Jr, Y. Urade, and J. W. Christman Induction and Function of Lipocalin Prostaglandin D Synthase in Host Immunity J. Immunol., August 15, 2007; 179(4): 2565 - 2575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, C. R. Woods, A. L. Mora, R. Joodi, K. L. Brigham, S. Iyer, and M. Rojas Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L131 - L141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-s. Cheng, W. Han, S. M. Chen, T. P. Sherrill, M. Chont, G.-Y. Park, J. R. Sheller, V. V. Polosukhin, J. W. Christman, F. E. Yull, et al. Airway Epithelium Controls Lung Inflammation and Injury through the NF-{kappa}B Pathway J. Immunol., May 15, 2007; 178(10): 6504 - 6513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. McCall and B. K. Yoza Gene Silencing in Severe Systemic Inflammation Am. J. Respir. Crit. Care Med., April 15, 2007; 175(8): 763 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Connelly, C. Robinson-Benion, M. Chont, L. Saint-Jean, H. Li, V. V. Polosukhin, T. S. Blackwell, and F. E. Yull A Transgenic Model Reveals Important Roles for the NF-{kappa}B Alternative Pathway (p100/p52) in Mammary Development and Links to Tumorigenesis J. Biol. Chem., March 30, 2007; 282(13): 10028 - 10035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhou, T. S. Blackwell, K. Goleniewska, J. F. O'Neal, G. A. FitzGerald, M. Lucitt, R. M. Breyer, and R. S. Peebles Jr. Prostaglandin I2 analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells J. Leukoc. Biol., March 1, 2007; 81(3): 809 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Eisenhut Effects of HSP70.1/3 gene knockout on NF-{kappa}B-mediated and cytokine-induced reduction in alveolar ion and fluid transport Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L365 - L365. [Full Text] [PDF]
|
|
|
|
|
|
M. Eisenhut Therapeutic Options for Pulmonary Edema Associated with Nuclear Factor-{kappa}B Activation in Septicemia. Am. J. Respir. Crit. Care Med., October 1, 2006; 174(7): 840b - 8841. [Full Text] [PDF]
|
|
|
|
|
|
M. Eisenhut Comment on "Duration and Intensity of NF-{kappa}B Activity Determine the Severity of Endotoxin-Induced Acute Lung Injury" J. Immunol., August 15, 2006; 177(4): 2038 - 2038. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
