| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Molecular Immunology and
Immunobiology, Immunex Corp., Seattle, WA 98101
The pleiotropic activities of the potent proinflammatory cytokine TNF are mediated by two structurally related, but functionally distinct, receptors, p55 and p75, that are coexpressed on most cell types. The majority of biologic responses classically attributed to TNF are mediated by p55. In contrast, p75 has been proposed to function as both a TNF antagonist by neutralizing TNF and as a TNF agonist by facilitating the interaction between TNF and p55 at the cell surface. We have examined the roles of p55 and p75 in mediating and modulating the activity of TNF in vivo by generating and examining mice genetically deficient in these receptors. Selective deficits in several host defense and inflammatory responses are observed in mice lacking p55 or both p55 and p75, but not in mice lacking p75. In these models, the activity of p55 is not impaired by the absence of p75, arguing against a physiologic role for p75 as an essential element of p55-mediated signaling. In contrast, exacerbated pulmonary inflammation and dramatically increased endotoxin induced serum TNF levels in mice lacking p75 suggest a dominant role for p75 in suppressing TNF-mediated inflammatory responses. In summary, these data help clarify the biologic roles of p55 and p75 in mediating and modulating the biologic activity of TNF and provide genetic evidence for an antagonistic role of p75 in vivo.
This article has been cited by other articles:
|
|
 |
|
  L. Kapas, S. G. Bohnet, T. R. Traynor, J. A. Majde, E. Szentirmai, P. Magrath, P. Taishi, and J. M. Krueger Spontaneous and influenza virus-induced sleep are altered in TNF-{alpha} double-receptor deficient mice J Appl Physiol, October 1, 2008; 105(4): 1187 - 1198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Shrestha, B. Zhang, W. E. Purtha, R. S. Klein, and M. S. Diamond Tumor Necrosis Factor Alpha Protects against Lethal West Nile Virus Infection by Promoting Trafficking of Mononuclear Leukocytes into the Central Nervous System J. Virol., September 15, 2008; 82(18): 8956 - 8964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Jessup, A. W. Brewer, M. Omori, E. A. Rickel, A. L. Budelsky, B.-R. P. Yoon, S. F. Ziegler, and M. R. Comeau Intradermal Administration of Thymic Stromal Lymphopoietin Induces a T Cell- and Eosinophil-Dependent Systemic Th2 Inflammatory Response J. Immunol., September 15, 2008; 181(6): 4311 - 4319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. McKarns and R. H. Schwartz Biphasic Regulation of Il2 Transcription in CD4+ T Cells: Roles for TNF-{alpha} Receptor Signaling and Chromatin Structure J. Immunol., July 15, 2008; 181(2): 1272 - 1281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Pryhuber, H. L. Huyck, S. Bhagwat, M. A. O'Reilly, J. N. Finkelstein, F. Gigliotti, and T. W. Wright Parenchymal Cell TNF Receptors Contribute to Inflammatory Cell Recruitment and Respiratory Failure in Pneumocystis carinii-Induced Pneumonia J. Immunol., July 15, 2008; 181(2): 1409 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Pan, C. Yu, H. Hsuchou, Y. Zhang, and A. J. Kastin Neuroinflammation facilitates LIF entry into brain: role of TNF Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1436 - C1442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Wert Does adiponectin play a role in pulmonary emphysema? Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1032 - L1034. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Elizur, T. L. Adair-Kirk, D. G. Kelley, G. L. Griffin, D. E. deMello, and R. M. Senior Tumor Necrosis Factor-{alpha} from Macrophages Enhances LPS-Induced Clara Cell Expression of Keratinocyte-Derived Chemokine Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 8 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Andrade Jr., T.A. Silva, G.A.B. Silva, A.L. Teixeira, and M.M. Teixeira The Role of Tumor Necrosis Factor Receptor Type 1 in Orthodontic Tooth Movement J. Dent. Res., November 1, 2007; 86(11): 1089 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zampetaki, L. Zeng, Q. Xiao, A. Margariti, Y. Hu, and Q. Xu Lacking cytokine production in ES cells and ES-cell-derived vascular cells stimulated by TNF-{alpha} is rescued by HDAC inhibitor trichostatin A Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1226 - C1238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Medeiros, J. R. Peixoto, A.-C. Oliveira, L. Cardilo-Reis, V. L. G. Koatz, L. Van Kaer, J. O. Previato, L. Mendonca-Previato, A. Nobrega, and M. Bellio Toll-like receptor 4 (TLR4)-dependent proinflammatory and immunomodulatory properties of the glycoinositolphospholipid (GIPL) from Trypanosoma cruzi J. Leukoc. Biol., September 1, 2007; 82(3): 488 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. He, Z. Zhong, K. Lindholm, L. Berning, W. Lee, C. Lemere, M. Staufenbiel, R. Li, and Y. Shen Deletion of tumor necrosis factor death receptor inhibits amyloid {beta} generation and prevents learning and memory deficits in Alzheimer's mice J. Cell Biol., August 27, 2007; 178(5): 829 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Wilson, M. E. Goddard, K. P. O'Dea, S. Choudhury, and M. Takata Differential roles of p55 and p75 tumor necrosis factor receptors on stretch-induced pulmonary edema in mice Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L60 - L68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Singh, M. Wuthrich, B. Klein, and M. Suresh Indirect Regulation of CD4 T-Cell Responses by Tumor Necrosis Factor Receptors in an Acute Viral Infection J. Virol., June 15, 2007; 81(12): 6502 - 6512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. M. Chandrasekharan, M. Siemionow, M. Unsal, L. Yang, E. Poptic, J. Bohn, K. Ozer, Z. Zhou, P. H. Howe, M. Penn, et al. Tumor necrosis factor {alpha} (TNF-{alpha}) receptor-II is required for TNF-{alpha}-induced leukocyte-endothelial interaction in vivo Blood, March 1, 2007; 109(5): 1938 - 1944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lundberg, P. V. Welander, C. K. Edwards III, N. van Rooijen, and E. Cantin Tumor Necrosis Factor (TNF) Protects Resistant C57BL/6 Mice against Herpes Simplex Virus-Induced Encephalitis Independently of Signaling via TNF Receptor 1 or 2 J. Virol., February 1, 2007; 81(3): 1451 - 1460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Greenfeld, K. F. Roby, M. E. Pepling, J. K. Babus, P. F. Terranova, and J. A. Flaws Tumor Necrosis Factor (TNF) Receptor Type 2 Is an Important Mediator of TNF alpha Function in the Mouse Ovary Biol Reprod, February 1, 2007; 76(2): 224 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bultinck, P. Sips, L. Vakaet, P. Brouckaert, and A. Cauwels Systemic NO production during (septic) shock depends on parenchymal and not on hematopoietic cells: in vivo iNOS expression pattern in (septic) shock FASEB J, November 1, 2006; 20(13): 2363 - 2365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Iosif, C. T. Ekdahl, H. Ahlenius, C. J. H. Pronk, S. Bonde, Z. Kokaia, S.-E. W. Jacobsen, and O. Lindvall Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J. Neurosci., September 20, 2006; 26(38): 9703 - 9712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Plumb, S McQuaid, A K Cross, J Surr, G Haddock, R A. Bunning, and M N Woodroofe Upregulation of ADAM-17 expression in active lesions in multiple sclerosis Multiple Sclerosis, August 1, 2006; 12(4): 375 - 385. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Scheuner, R. Patel, F. Wang, K. Lee, K. Kumar, J. Wu, A. Nilsson, M. Karin, and R. J. Kaufman Double-stranded RNA-dependent Protein Kinase Phosphorylation of the {alpha}-Subunit of Eukaryotic Translation Initiation Factor 2 Mediates Apoptosis J. Biol. Chem., July 28, 2006; 281(30): 21458 - 21468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. D'hulst, K. R. Bracke, T. Maes, J. L. De Bleecker, R. A. Pauwels, G. F. Joos, and G. G. Brusselle Role of tumour necrosis factor-{alpha} receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema Eur. Respir. J., July 1, 2006; 28(1): 102 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Seymour, J. P. Sundberg, and H. HogenEsch Abnormal lymphoid organ development in immunodeficient mutant mice. Vet. Pathol., July 1, 2006; 43(4): 401 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rutschmann, K. Hoebe, J. Zalevsky, X. Du, N. Mann, B. I. Dahiyat, P. Steed, and B. Beutler PanR1, a Dominant Negative Missense Allele of the Gene Encoding TNF-{alpha} (Tnf), Does Not Impair Lymphoid Development. J. Immunol., June 15, 2006; 176(12): 7525 - 7532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Liepinsh, S. I. Grivennikov, K. D. Klarmann, M. A. Lagarkova, M. S. Drutskaya, S. J. Lockett, L. Tessarollo, M. McAuliffe, J. R. Keller, D. V. Kuprash, et al. Novel Lymphotoxin Alpha (LT{alpha}) Knockout Mice with Unperturbed Tumor Necrosis Factor Expression: Reassessing LT{alpha} Biological Functions. Mol. Cell. Biol., June 1, 2006; 26(11): 4214 - 4225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Garton, P. J. Gough, and E. W. Raines Emerging roles for ectodomain shedding in the regulation of inflammatory responses J. Leukoc. Biol., June 1, 2006; 79(6): 1105 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nagashima, V. G. Sasseville, D. Wen, A. Bielecki, H. Yang, C. Simpson, E. Grant, M. Hepperle, G. Harriman, B. Jaffee, et al. Rapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical inhibitor of IKKbeta Blood, June 1, 2006; 107(11): 4266 - 4273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ismail, H. L. Stevenson, and D. H. Walker Role of Tumor Necrosis Factor Alpha (TNF-{alpha}) and Interleukin-10 in the Pathogenesis of Severe Murine Monocytotropic Ehrlichiosis: Increased Resistance of TNF Receptor p55- and p75-Deficient Mice to Fatal Ehrlichial Infection Infect. Immun., March 1, 2006; 74(3): 1846 - 1856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Tavener and P. Kubes Cellular and molecular mechanisms underlying LPS-associated myocyte impairment Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H800 - H806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Smookler, F. F. Mohammed, Z. Kassiri, G. S. Duncan, T. W. Mak, and R. Khokha Cutting Edge: Tissue Inhibitor of Metalloproteinase 3 Regulates TNF-Dependent Systemic Inflammation J. Immunol., January 15, 2006; 176(2): 721 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Kim, J. J. Priatel, S.-J. Teh, and H.-S. Teh TNF Receptor Type 2 (p75) Functions as a Costimulator for Antigen-Driven T Cell Responses In Vivo J. Immunol., January 15, 2006; 176(2): 1026 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Hutson Physiologic Interactions Between Macrophages and Leydig Cells Experimental Biology and Medicine, January 1, 2006; 231(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Nollert, I. Schwabenland, D. Maktav, F. Kur, F. Christ, P. Fraunberger, B. Reichart, and C. Vicol Miniaturized Cardiopulmonary Bypass in Coronary Artery Bypass Surgery: Marginal Impact on Inflammation and Coagulation but Loss of Safety Margins Ann. Thorac. Surg., December 1, 2005; 80(6): 2326 - 2332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Calder, L. B. Nicholson, and A. D. Dick A Selective Role for the TNF p55 Receptor in Autocrine Signaling following IFN-{gamma} Stimulation in Experimental Autoimmune Uveoretinitis J. Immunol., November 15, 2005; 175(10): 6286 - 6293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. O'Dea, A. J. Young, H. Yamamoto, J. L. Robotham, F. M. Brennan, and M. Takata Lung-marginated Monocytes Modulate Pulmonary Microvascular Injury during Early Endotoxemia Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1119 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Barber, M. Fazzari, and J. W. Pollard Th1 Cytokines Are Essential for Placental Immunity to Listeria monocytogenes Infect. Immun., October 1, 2005; 73(10): 6322 - 6331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Sternlicht, S. W. Sunnarborg, H. Kouros-Mehr, Y. Yu, D. C. Lee, and Z. Werb Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin Development, September 1, 2005; 132(17): 3923 - 3933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bernardino, S. Xapelli, A. P. Silva, B. Jakobsen, F. R. Poulsen, C. R. Oliveira, A. Vezzani, J. O. Malva, and J. Zimmer Modulator Effects of Interleukin-1{beta} and Tumor Necrosis Factor-{alpha} on AMPA-Induced Excitotoxicity in Mouse Organotypic Hippocampal Slice Cultures J. Neurosci., July 20, 2005; 25(29): 6734 - 6744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Gilbert, J. Rubin, and M. S. Nanes The p55 TNF receptor mediates TNF inhibition of osteoblast differentiation independently of apoptosis Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E1011 - E1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Wilson, S. Choudhury, and M. Takata Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L599 - L607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S.M. Boesten, A. S. M. Zadelaar, A. van Nieuwkoop, M. J.J. Gijbels, M. P.J. de Winther, L. M. Havekes, and B. J.M. van Vlijmen Tumor necrosis factor-{alpha} promotes atherosclerotic lesion progression in APOE*3-leiden transgenic mice Cardiovasc Res, April 1, 2005; 66(1): 179 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Meng, L. Ao, Y. Song, C. D. Raeburn, D. A. Fullerton, and A. H. Harken Signaling for myocardial depression in hemorrhagic shock: roles of Toll-like receptor 4 and p55 TNF-{alpha} receptor Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R600 - R606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Till, P. Rosenstiel, A. Krippner-Heidenreich, S. Mascheretti-Croucher, P. J. P. Croucher, H. Schafer, P. Scheurich, D. Seegert, and S. Schreiber The Met-196 -> Arg Variation of Human Tumor Necrosis Factor Receptor 2 (TNFR2) Affects TNF-{alpha}-induced Apoptosis by Impaired NF-{kappa}B Signaling and Target Gene Expression J. Biol. Chem., February 18, 2005; 280(7): 5994 - 6004. [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]
|
|
|
|
|
|
M. Suresh, A. Singh, and C. Fischer Role of Tumor Necrosis Factor Receptors in Regulating CD8 T-Cell Responses during Acute Lymphocytic Choriomeningitis Virus Infection J. Virol., January 1, 2005; 79(1): 202 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fairweather, S. Frisancho-Kiss, S. A. Yusung, M. A. Barrett, S. E. Davis, R. A. Steele, S. J. L. Gatewood, and N. R. Rose IL-12 Protects against Coxsackievirus B3-Induced Myocarditis by Increasing IFN-{gamma} and Macrophage and Neutrophil Populations in the Heart J. Immunol., January 1, 2005; 174(1): 261 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Liu, D. Xu, H. Yang, H. Xu, Z. Shi, X. Cao, S. Takeshita, J. Liu, M. Teale, and X. Feng Functional Identification of Three Receptor Activator of NF-{kappa}B Cytoplasmic Motifs Mediating Osteoclast Differentiation and Function J. Biol. Chem., December 24, 2004; 279(52): 54759 - 54769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Zheng, Q.-L. Cheng, A.-R. Plati, S. Q. Ye, M. Berho, A. Banerjee, M. Potier, E. A. Jaimes, H. Yu, Y.-F. Guan, et al. The Glomerulosclerosis of Aging in Females: Contribution of the Proinflammatory Mesangial Cell Phenotype to Macrophage Infiltration Am. J. Pathol., November 1, 2004; 165(5): 1789 - 1798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alikhani, Z. Alikhani, and D.T. Graves Apoptotic Effects of LPS on Fibroblasts are Indirectly Mediated through TNFR1 J. Dent. Res., September 1, 2004; 83(9): 671 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xanthoulea, M. Pasparakis, S. Kousteni, C. Brakebusch, D. Wallach, J. Bauer, H. Lassmann, and G. Kollias Tumor Necrosis Factor (TNF) Receptor Shedding Controls Thresholds of Innate Immune Activation That Balance Opposing TNF Functions in Infectious and Inflammatory Diseases J. Exp. Med., August 2, 2004; 200(3): 367 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Niederkorn, E. Mayhew, J. Mellon, and S. Hegde Role of Tumor Necrosis Factor Receptor Expression in Anterior Chamber-Associated Immune Deviation (ACAID) and Corneal Allograft Survival Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2674 - 2681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Yankee, T. J. Yun, K. E. Draves, K. Ganesh, M. J. Bevan, K. Murali-Krishna, and E. A. Clark The Gads (GrpL) Adaptor Protein Regulates T Cell Homeostasis J. Immunol., August 1, 2004; 173(3): 1711 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamamoto, M.-N. Kweon, P. D. Rennert, T. Hiroi, K. Fujihashi, J. R. McGhee, and H. Kiyono Role of Gut-Associated Lymphoreticular Tissues in Antigen-Specific Intestinal IgA Immunity J. Immunol., July 15, 2004; 173(2): 762 - 769. [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. Suresh, X. Gao, C. Fischer, N. E. Miller, and K. Tewari Dissection of Antiviral and Immune Regulatory Functions of Tumor Necrosis Factor Receptors in a Chronic Lymphocytic Choriomeningitis Virus Infection J. Virol., April 15, 2004; 78(8): 3906 - 3918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Wright, G. S. Pryhuber, P. R. Chess, Z. Wang, R. H. Notter, and F. Gigliotti TNF Receptor Signaling Contributes to Chemokine Secretion, Inflammation, and Respiratory Deficits during Pneumocystis Pneumonia J. Immunol., February 15, 2004; 172(4): 2511 - 2521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Krueger and K. Callis Potential of Tumor Necrosis Factor Inhibitors in Psoriasis and Psoriatic Arthritis Arch Dermatol, February 1, 2004; 140(2): 218 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Riehl, R. D. Newberry, R. G. Lorenz, and W. F. Stenson TNFR1 mediates the radioprotective effects of lipopolysaccharide in the mouse intestine Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G166 - G173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
