The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Differential activation and antagonistic function of HIF-α isoforms in macrophages are essential for NO homeostasis
Open accessAbstract
Hypoxic response and inflammation both involve the action of the hypoxia-inducible transcription factors HIF-1α and HIF-2α. Previous studies have revealed that both HIF-α proteins are in a number of aspects similarly regulated post-translationally. However, the functional interrelationship of these two isoforms remains largely unclear. The polarization of macrophages controls functionally divergent processes; one of these is nitric oxide (NO) production, which in turn is controlled in part by HIF factors. We show here that the HIF-α isoforms can be differentially activated: HIF-1α is induced by Th1 cytokines in M1 macrophage polarization, whereas HIF-2α is induced by Th2 cytokines during an M2 response. This differential response was most evident in polarized macrophages through HIF-α isoform-specific regulation of the inducible NO synthase gene by HIF-1α, and the arginase1 gene by HIF-2α. In silico modeling predicted that regulation of overall NO availability is due to differential regulation of HIF-1α versus HIF-2α, acting to, respectively, either increase or suppress NO synthesis. An in vivo model of endotoxin challenge confirmed this; thus, these studies reveal that the two homologous transcription factors, HIF-1α and HIF-2α, can have physiologically antagonistic functions, but that their antiphase regulation allows them to coordinately regulate NO production in a cytokine-induced and transcription-dependent fashion.
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Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Arginine metabolism: nitric oxide and beyond
WU, G., & MORRIS, S. M. (1998) · Biochemical Journal · doi:10.1042/bj3360001 · Cited by 2,811
Macrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107
Stein, M., Keshav, S., Harris, N., & Gordon, S. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.1.287 · Cited by 1,960
Regulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775
NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α
Rius, J., Guma, M., Schachtrup, C., Akassoglou, K., Zinkernagel, A. S., Nizet, V., Johnson, R. S., Haddad, G. G., & Karin, M. (2008) · Nature · doi:10.1038/nature06905 · Cited by 1,614
Self-citationTie2-Cre Transgenic Mice: A New Model for Endothelial Cell-Lineage Analysis in Vivo
Kisanuki, Y. Y., Hammer, R. E., Miyazaki, J.-I., Williams, S. C., Richardson, J. A., & Yanagisawa, M. (2001) · Developmental Biology · doi:10.1006/dbio.2000.0106 · Cited by 1,241
Weidemann, A., & Johnson, R. S. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.12 · Cited by 941
Self-citationRegulation of hypoxia-inducible factor-1α by NF-κB
van Uden, P., Kenneth, N. S., & Rocha, S. (2008) · Biochemical Journal · doi:10.1042/bj20080476 · Cited by 729
Interdependence of hypoxic and innate immune responses
Nizet, V., & Johnson, R. S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2607 · Cited by 708
Self-citationEl Kasmi, K. C., Qualls, J. E., Pesce, J. T., Smith, A. M., Thompson, R. W., Henao-Tamayo, M., Basaraba, R. J., König, T., Schleicher, U., Koo, M.-S., et al. (2008) · Nature Immunology · doi:10.1038/ni.1671 · Cited by 646
Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo
Rankin, E. B., Biju, M. P., Liu, Q., Unger, T. L., Rha, J., Johnson, R. S., Simon, M. C., Keith, B., & Haase, V. H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30117 · Cited by 596
Self-citationARGINASE: A CRITICAL REGULATOR OF NITRIC OXIDE SYNTHESIS AND VASCULAR FUNCTION
Durante, W., Johnson, F. K., & Johnson, R. A. (2007) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2007.04638.x · Cited by 577
Self-citationHypoxia Regulates Macrophage Functions in Inflammation
Murdoch, C., Muthana, M., & Lewis, C. E. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6257 · Cited by 455
Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-κB
Frede, S., Stockmann, C., Freitag, P., & Fandrey, J. (2006) · Biochemical Journal · doi:10.1042/bj20051839 · Cited by 436
Self-citationKrieg, M., Haas, R., Brauch, H., Acker, T., Flamme, I., & Plate, K. H. (2000) · Oncogene · doi:10.1038/sj.onc.1203938 · Cited by 396
HIF2α inhibition promotes p53 pathway activity, tumor cell death, and radiation responses
Bertout, J. A., Majmundar, A. J., Gordan, J. D., Lam, J. C., Ditsworth, D., Keith, B., Brown, E. J., Nathanson, K. L., & Simon, M. C. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907357106 · Cited by 196
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Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632
Hypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
Self-citationMetabolic reprogramming in macrophages and dendritic cells in innate immunity
Kelly, B., & O'Neill, L. A. (2015) · Cell Research · doi:10.1038/cr.2015.68 · Cited by 1,876
Metadata
- Authors
- Takeda, N., O'Dea, E. L., Doedens, A., Kim, J.-W., Weidemann, A., Stockmann, C., Asagiri, M., Simon, M. C., Hoffmann, A., & Johnson, R. S.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-03-01
- Volume
- 24
- Issue
- 5
- Pages
- 491-501
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W1981253971
- Cited by
- 623
- References
- 21
- Type
- posted content
- Language
- en
- Open access
- diamond
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