| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B in Leukocyte Recruitment1
*
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
Physiology Program, Harvard School of Public Health, Boston, MA 02115;
Division of Immunology Research, Department of Pathology, Brigham and Women’s Hospital, and Division of Emergency Medicine, Children’s Hospital, Boston, MA 02115;
Department of Pathology, Tufts University School of Medicine and Veterinary Medicine, Boston MA 02111;
¶ Department of Biological Sciences, Columbia University, New York, NY 10027;
||
Biogen, Cambridge, MA 02142;
#
California Institute of Technology, Pasadena, CA 91125.
NF-
B binding sites are present in the promoter regions of many
acute phase and inflammatory response genes, suggesting that NF-B
plays an important role in the initiation of innate immune responses.
However, targeted mutations of the various NF-B family members have
yet to identify members responsible for this critical role.
RelA-deficient mice die on embryonic day 15 from TNF-
-induced liver
degeneration. To investigate the importance of RelA in innate immunity,
we genetically suppressed this embryonic lethality by breeding the RelA
deficiency onto a TNFR type 1 (TNFR1)-deficient background.
TNFR1/RelA-deficient mice were born healthy, but were susceptible to
bacterial infections and bacteremia and died within a few weeks after
birth. Hemopoiesis was intact in TNFR1/RelA-deficient newborns, but
neutrophil emigration to alveoli during LPS-induced pneumonia was
severely reduced relative to that in wild-type or TNFR1-deficient mice.
In contrast, radiation chimeras reconstituted with RelA or
TNFR1/RelA-deficient hemopoietic cells were healthy and demonstrated no
defect in neutrophil emigration during LPS-induced pneumonia. Analysis
of RNA harvested from the lungs of mice 4 h after LPS insufflation
revealed that the induction of several genes important for neutrophil
recruitment to the lung was significantly reduced in
TNFR1/RelA-deficient mice relative to that in wild-type or
TNFR1-deficient mice. These results suggest that TNFR1-independent
activation of RelA is essential in cells of nonhemopoietic origin
during the initiation of an innate immune
response.
This article has been cited by other articles:
|
|
 |
|
  L. J. Quinton, M. R. Jones, B. E. Robson, and J. P. Mizgerd Mechanisms of the Hepatic Acute-Phase Response during Bacterial Pneumonia Infect. Immun., June 1, 2009; 77(6): 2417 - 2426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wang, I. Paz-Priel, and A. D. Friedman NF-{kappa}B p50 Regulates C/EBP{alpha} Expression and Inflammatory Cytokine-Induced Neutrophil Production J. Immunol., May 1, 2009; 182(9): 5757 - 5762. [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]
|
|
|
|
|
|
A. Craig, J. Mai, S. Cai, and S. Jeyaseelan Neutrophil Recruitment to the Lungs during Bacterial Pneumonia Infect. Immun., February 1, 2009; 77(2): 568 - 575. [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Schulteis, H. Chu, X. Dai, Y. Chen, B. Edwards, D. Haribhai, C. B. Williams, S. Malarkannan, M. J. Hessner, S. Glisic-Milosavljevic, et al. Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5 Blood, December 15, 2008; 112(13): 4905 - 4914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xu, F. Fang, D. K. St. Clair, P. Sompol, S. Josson, and W. H. St. Clair SN52, a novel nuclear factor-{kappa}B inhibitor, blocks nuclear import of RelB:p52 dimer and sensitizes prostate cancer cells to ionizing radiation Mol. Cancer Ther., August 1, 2008; 7(8): 2367 - 2376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gratz, M. Siller, B. Schaljo, Z. A. Pirzada, I. Gattermeier, I. Vojtek, C. J. Kirschning, H. Wagner, S. Akira, E. Charpentier, et al. Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9 J. Biol. Chem., July 18, 2008; 283(29): 19879 - 19887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. V. Kravchenko, G. F. Kaufmann, J. C. Mathison, D. A. Scott, A. Z. Katz, D. C. Grauer, M. Lehmann, M. M. Meijler, K. D. Janda, and R. J. Ulevitch Modulation of Gene Expression via Disruption of NF-{kappa}B Signaling by a Bacterial Small Molecule Science, July 11, 2008; 321(5886): 259 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dong, E. Jimi, H. Zhong, M. S. Hayden, and S. Ghosh Repression of gene expression by unphosphorylated NF-{kappa}B p65 through epigenetic mechanisms Genes & Dev., May 1, 2008; 22(9): 1159 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Simmonds and B. M. Foxwell Signalling, inflammation and arthritis: NF-{kappa}B and its relevance to arthritis and inflammation Rheumatology, May 1, 2008; 47(5): 584 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vaira, T. Johnson, A. C. Hirbe, M. Alhawagri, I. Anwisye, B. Sammut, J. O'Neal, W. Zou, K. N. Weilbaecher, R. Faccio, et al. RelB is the NF-{kappa}B subunit downstream of NIK responsible for osteoclast differentiation PNAS, March 11, 2008; 105(10): 3897 - 3902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Mizgerd Acute Lower Respiratory Tract Infection N. Engl. J. Med., February 14, 2008; 358(7): 716 - 727. [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Kelly, K. McNagny, D. L. Williams, N. van Rooijen, L. Maxwell, C. Gwozd, C. H. Mody, and P. Kubes The Lung Responds to Zymosan in a Unique Manner Independent of Toll-Like Receptors, Complement, and Dectin-1 Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 227 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. V. Groesdonk, F. Wagner, B. Hoffarth, M. Georgieff, and U. Senftleben Enhancement of NF-{kappa}B Activation in Lymphocytes Prevents T Cell Apoptosis and Improves Survival in Murine Sepsis J. Immunol., December 15, 2007; 179(12): 8083 - 8089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wullaert, G. van Loo, K. Heyninck, and R. Beyaert Hepatic Tumor Necrosis Factor Signaling and Nuclear Factor-{kappa}B: Effects on Liver Homeostasis and Beyond Endocr. Rev., June 1, 2007; 28(4): 365 - 386. [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]
|
|
|
|
 |
|
 H.-Y. Cho, D. L. Morgan, A. K. Bauer, and S. R. Kleeberger Signal Transduction Pathways of Tumor Necrosis Factor-mediated Lung Injury Induced by Ozone in Mice Am. J. Respir. Crit. Care Med., April 15, 2007; 175(8): 829 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Quinton, M. R. Jones, B. T. Simms, M. S. Kogan, B. E. Robson, S. J. Skerrett, and J. P. Mizgerd Functions and Regulation of NF-{kappa}B RelA during Pneumococcal Pneumonia J. Immunol., February 1, 2007; 178(3): 1896 - 1903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bhattacharyya, D. Mandal, G. S. Sen, S. Pal, S. Banerjee, L. Lahiry, J. H. Finke, C. S. Tannenbaum, T. Das, and G. Sa Tumor-Induced Oxidative Stress Perturbs Nuclear Factor-{kappa}B Activity-Augmenting Tumor Necrosis Factor-{alpha}-Mediated T-Cell Death: Protection by Curcumin Cancer Res., January 1, 2007; 67(1): 362 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. V. Groesdonk, S. Schlottmann, F. Richter, M. Georgieff, and U. Senftleben Escherichia coli Prevents Phagocytosis-Induced Death of Macrophages via Classical NF-{kappa}B Signaling, a Link to T-Cell Activation. Infect. Immun., October 1, 2006; 74(10): 5989 - 6000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Prince, J. P. Mizgerd, J. Wiener-Kronish, and J. Bhattacharya Cell signaling underlying the pathophysiology of pneumonia Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L297 - L300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Igarashi, Y. Baba, Y. Nagai, E. Jimi, S. Ghosh, and P. W Kincade NF-{kappa}B is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNF{alpha} Int. Immunol., May 1, 2006; 18(5): 653 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Everhart, W. Han, T. P. Sherrill, M. Arutiunov, V. V. Polosukhin, J. R. Burke, R. T. Sadikot, J. W. Christman, F. E. Yull, and T. S. Blackwell Duration and Intensity of NF-{kappa}B Activity Determine the Severity of Endotoxin-Induced Acute Lung Injury. J. Immunol., April 15, 2006; 176(8): 4995 - 5005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Matsuyama, M. Watanabe, Y. Shirahama, H. Mitsuyama, I. Higashimoto, M. Osame, and K. Arimura Discoidin Domain Receptor 1 Contributes to the Survival of Lung Fibroblast in Idiopathic Pulmonary Fibrosis Am. J. Pathol., March 1, 2006; 168(3): 866 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mookherjee, K. L. Brown, D. M. E. Bowdish, S. Doria, R. Falsafi, K. Hokamp, F. M. Roche, R. Mu, G. H. Doho, J. Pistolic, et al. Modulation of the TLR-Mediated Inflammatory Response by the Endogenous Human Host Defense Peptide LL-37 J. Immunol., February 15, 2006; 176(4): 2455 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Jones, B. T. Simms, M. M. Lupa, M. S. Kogan, and J. P. Mizgerd Lung NF-{kappa}B Activation and Neutrophil Recruitment Require IL-1 and TNF Receptor Signaling during Pneumococcal Pneumonia J. Immunol., December 1, 2005; 175(11): 7530 - 7535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M Lindstrom and P. R Bennett The role of nuclear factor kappa B in human labour Reproduction, November 1, 2005; 130(5): 569 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hachem and R. B. Gartenhaus Oncogenes as molecular targets in lymphoma Blood, September 15, 2005; 106(6): 1911 - 1923. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Zhang, S. Tao, R. Kimmel, and P. A. Khavari CDK4 regulation by TNFR1 and JNK is required for NF-{kappa}B-mediated epidermal growth control J. Cell Biol., February 14, 2005; 168(4): 561 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cataisson, A. J. Pearson, S. Torgerson, S. A. Nedospasov, and S. H. Yuspa Protein Kinase C{alpha}-Mediated Chemotaxis of Neutrophils Requires NF-{kappa}B Activity but Is Independent of TNF{alpha} Signaling in Mouse Skin In Vivo J. Immunol., February 1, 2005; 174(3): 1686 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, R. A. Barke, R. Charboneau, and S. Roy Morphine Impairs Host Innate Immune Response and Increases Susceptibility to Streptococcus pneumoniae Lung Infection J. Immunol., January 1, 2005; 174(1): 426 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gadjeva, M. F. Tomczak, M. Zhang, Y. Y. Wang, K. Dull, A. B. Rogers, S. E. Erdman, J. G. Fox, M. Carroll, and B. H. Horwitz A Role for NF-{kappa}B Subunits p50 and p65 in the Inhibition of Lipopolysaccharide-Induced Shock J. Immunol., November 1, 2004; 173(9): 5786 - 5793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Papa, F. Zazzeroni, C. G. Pham, C. Bubici, and G. Franzoso Linking JNK signaling to NF-{kappa}B: a key to survival J. Cell Sci., October 15, 2004; 117(22): 5197 - 5208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Cavin, M. Venkatraman, V. M. Factor, S. Kaur, I. Schroeder, F. Mercurio, A. A. Beg, S. S. Thorgeirsson, and M. Arsura Regulation of {alpha}-Fetoprotein by Nuclear Factor-{kappa}B Protects Hepatocytes from Tumor Necrosis Factor-{alpha} Cytotoxicity during Fetal Liver Development and Hepatic Oncogenesis Cancer Res., October 1, 2004; 64(19): 7030 - 7038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Hayden and S. Ghosh Signaling to NF-{kappa}B Genes & Dev., September 15, 2004; 18(18): 2195 - 2224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gugasyan, A. Voss, G. Varigos, T. Thomas, R. J. Grumont, P. Kaur, G. Grigoriadis, and S. Gerondakis The Transcription Factors c-rel and RelA Control Epidermal Development and Homeostasis in Embryonic and Adult Skin via Distinct Mechanisms Mol. Cell. Biol., July 1, 2004; 24(13): 5733 - 5745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Skerrett, H. D. Liggitt, A. M. Hajjar, R. K. Ernst, S. I. Miller, and C. B. Wilson Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L143 - L152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Mizgerd, M. M. Lupa, J. Hjoberg, J. C. Vallone, H. B. Warren, J. P. Butler, and E. S. Silverman Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1 Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1302 - L1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Thornton, D. Kudo, P. Rayman, C. Horton, L. Molto, M. K. Cathcart, C. Ng, E. Paszkiewicz-Kozik, R. Bukowski, I. Derweesh, et al. Degradation of NF-{kappa}B in T Cells by Gangliosides Expressed on Renal Cell Carcinomas J. Immunol., March 15, 2004; 172(6): 3480 - 3490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Vasudevan, S. Gurumurthy, and V. M. Rangnekar Suppression of PTEN Expression by NF-{kappa}B Prevents Apoptosis Mol. Cell. Biol., February 1, 2004; 24(3): 1007 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Zhang, C. L. Green, S. Tao, and P. A. Khavari NF-{kappa}B RelA opposes epidermal proliferation driven by TNFR1 and JNK Genes & Dev., January 1, 2004; 18(1): 17 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Prendes, Y. Zheng, and A. A. Beg Regulation of Developing B Cell Survival by RelA-Containing NF-{kappa}B Complexes J. Immunol., October 15, 2003; 171(8): 3963 - 3969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Mizgerd, M. M. Lupa, M. S. Kogan, H. B. Warren, L. Kobzik, and G. P. Topulos Nuclear Factor-{kappa}B p50 Limits Inflammation and Prevents Lung Injury during Escherichia coli Pneumonia Am. J. Respir. Crit. Care Med., October 1, 2003; 168(7): 810 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Poynter, C. G. Irvin, and Y. M. W. Janssen-Heininger A Prominent Role for Airway Epithelial NF-{kappa}B Activation in Lipopolysaccharide-Induced Airway Inflammation J. Immunol., June 15, 2003; 170(12): 6257 - 6265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-W. Li, S. A. Omori, T. Labuda, M. Karin, and R. C. Rickert IKK{beta} Is Required for Peripheral B Cell Survival and Proliferation J. Immunol., May 1, 2003; 170(9): 4630 - 4637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Mizgerd, M. L. Scott, M. R. Spieker, and C. M. Doerschuk Functions of I{kappa}B Proteins in Inflammatory Responses to Escherichia coli LPS in Mouse Lungs Am. J. Respir. Cell Mol. Biol., November 1, 2002; 27(5): 575 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Caamano and C. A. Hunter NF-{kappa}B Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions Clin. Microbiol. Rev., July 1, 2002; 15(3): 414 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Alcamo, N. Hacohen, L. C. Schulte, P. D. Rennert, R. O. Hynes, and D. Baltimore Requirement for the NF-{kappa}B Family Member RelA in the Development of Secondary Lymphoid Organs J. Exp. Med., January 22, 2002; 195(2): 233 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Silverman and T. Maniatis NF-{kappa}B signaling pathways in mammalian and insect innate immunity Genes & Dev., September 15, 2001; 15(18): 2321 - 2342. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
