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Published in: Inflammation 3/2016

01-06-2016 | REVIEW

Hypoxia-Inducible Factor-1α and Autoimmune Lupus, Arthritis

Authors: Zu-Cheng Yang, Yi Liu

Published in: Inflammation | Issue 3/2016

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Abstract

Hypoxia elicits an orchestrated response in cells, tissues, and entire organisms to survive a hypoxic challenge. On a molecular level, this response can be controlled by oxygen-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF)-1α. Recently, studies have shown that HIF-1α plays an important role in the development and function of T helper (Th) cells, regulatory T (Treg) cells, and dendritic cells (DCs). Because these cells are critical in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, the roles of HIF-1α in these autoimmune disorders cannot be neglected. In this review, we discuss recent findings on the important roles of HIF-1α in immune cells and the possible pathologic roles of HIF-1α in autoimmune diseases. The obtained information may lead to deeper insights into the roles of HIF-1α in these disorders.
Literature
1.
go back to reference Dehne, N., and B. Brüne. 2009. HIF-1 in the inflammatory microenvironment. Experimental Cell Research 315: 1791–1797.CrossRefPubMed Dehne, N., and B. Brüne. 2009. HIF-1 in the inflammatory microenvironment. Experimental Cell Research 315: 1791–1797.CrossRefPubMed
2.
go back to reference Semenza, G.L. 1999. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annual Review of Cell and Developmental Biology 15: 551–578.CrossRefPubMed Semenza, G.L. 1999. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annual Review of Cell and Developmental Biology 15: 551–578.CrossRefPubMed
3.
go back to reference Pugh, C.W., G.W. Chang, M. Cockman, A.C. Epstein, J.M. Gleadle, P.H. Maxwell, et al. 1999. Regulation of gene expression by oxygen levels in mammalian cells. Advances in Nephrology from the Necker Hospital 29: 191–206.PubMed Pugh, C.W., G.W. Chang, M. Cockman, A.C. Epstein, J.M. Gleadle, P.H. Maxwell, et al. 1999. Regulation of gene expression by oxygen levels in mammalian cells. Advances in Nephrology from the Necker Hospital 29: 191–206.PubMed
4.
go back to reference Sowter, H.M., P.J. Ratcliffe, P. Watson, A.H. Greenberg, and A.L. Harris. 2001. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Research 61: 6669–6673.PubMed Sowter, H.M., P.J. Ratcliffe, P. Watson, A.H. Greenberg, and A.L. Harris. 2001. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Research 61: 6669–6673.PubMed
5.
go back to reference Keith, B., R.S. Johnson, and M.C. Simon. 2011. HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression. Nature Reviews in Cancer 12: 9–22.PubMed Keith, B., R.S. Johnson, and M.C. Simon. 2011. HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression. Nature Reviews in Cancer 12: 9–22.PubMed
6.
go back to reference Forristal, C.E., K.L. Wright, N.A. Hanley, R.O. Oreffo, and F.D. Houghton. 2010. Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction 139: 85–97.CrossRefPubMedPubMedCentral Forristal, C.E., K.L. Wright, N.A. Hanley, R.O. Oreffo, and F.D. Houghton. 2010. Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction 139: 85–97.CrossRefPubMedPubMedCentral
7.
go back to reference Clambey, E.T., E.N. McNamee, J.A. Westrich, L.E. Glover, E.L. Campbell, P. Jedlicka, et al. 2012. Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa. Proceedings of the National Academy of Sciences of the United States of America 109: E2784–E2793.CrossRefPubMedPubMedCentral Clambey, E.T., E.N. McNamee, J.A. Westrich, L.E. Glover, E.L. Campbell, P. Jedlicka, et al. 2012. Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa. Proceedings of the National Academy of Sciences of the United States of America 109: E2784–E2793.CrossRefPubMedPubMedCentral
8.
go back to reference Ben-Shoshan, J., S. Maysel-Auslender, A. Mor, G. Keren, and J. George. 2008. Hypoxia controls CD4 + CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1alpha. European Journal of Immunology 38: 2412–2418.CrossRefPubMed Ben-Shoshan, J., S. Maysel-Auslender, A. Mor, G. Keren, and J. George. 2008. Hypoxia controls CD4 + CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1alpha. European Journal of Immunology 38: 2412–2418.CrossRefPubMed
9.
go back to reference Wu, J., H. Cui, Z. Zhu, L. Wang, H. Li, and D. Wang. 2014. Effect of HIF1α on Foxp3 expression in CD4+ CD25− T lymphocytes. Microbiology and Immunology 58: 409–415.CrossRefPubMed Wu, J., H. Cui, Z. Zhu, L. Wang, H. Li, and D. Wang. 2014. Effect of HIF1α on Foxp3 expression in CD4+ CD25− T lymphocytes. Microbiology and Immunology 58: 409–415.CrossRefPubMed
10.
go back to reference Shi, L.Z., R. Wang, G. Huang, P. Vogel, G. Neale, D.R. Green, et al. 2011. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. Journal of Experimental Medicine 208: 1367–1376.CrossRefPubMedPubMedCentral Shi, L.Z., R. Wang, G. Huang, P. Vogel, G. Neale, D.R. Green, et al. 2011. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. Journal of Experimental Medicine 208: 1367–1376.CrossRefPubMedPubMedCentral
11.
go back to reference Filippi, I., E. Morena, C. Aldinucci, F. Carraro, S. Sozzani, and A. Naldini. 2014. Short-term hypoxia enhances the migratory capability of dendritic cell through HIF-1α and PI3K/Akt pathway. Journal of Cellular Physiology 229: 2067–2076.CrossRefPubMed Filippi, I., E. Morena, C. Aldinucci, F. Carraro, S. Sozzani, and A. Naldini. 2014. Short-term hypoxia enhances the migratory capability of dendritic cell through HIF-1α and PI3K/Akt pathway. Journal of Cellular Physiology 229: 2067–2076.CrossRefPubMed
12.
go back to reference Köhler, T., B. Reizis, R.S. Johnson, H. Weighardt, and I. Förster. 2012. Influence of hypoxia-inducible factor 1α on dendritic cell differentiation and migration. European Journal of Immunology 42: 1226–1236.CrossRefPubMed Köhler, T., B. Reizis, R.S. Johnson, H. Weighardt, and I. Förster. 2012. Influence of hypoxia-inducible factor 1α on dendritic cell differentiation and migration. European Journal of Immunology 42: 1226–1236.CrossRefPubMed
13.
go back to reference Jantsch, J., D. Chakravortty, N. Turza, A.T. Prechtel, B. Buchholz, R.G. Gerlach, et al. 2008. Hypoxia and hypoxia-inducible factor-1 alpha modulate lipopolysaccharide-induced dendritic cell activation and function. Journal of Immunology 180: 4697–4705.CrossRef Jantsch, J., D. Chakravortty, N. Turza, A.T. Prechtel, B. Buchholz, R.G. Gerlach, et al. 2008. Hypoxia and hypoxia-inducible factor-1 alpha modulate lipopolysaccharide-induced dendritic cell activation and function. Journal of Immunology 180: 4697–4705.CrossRef
14.
go back to reference Ma, C., J. Wei, F. Zhan, R. Wang, K. Fu, X. Wan, et al. 2012. Urinary hypoxia-inducible factor-1 alpha levels are associated with histologic chronicity changes and renal function in patients with lupus nephritis. Yonsei Medical Journal 53: 587–592.CrossRefPubMedPubMedCentral Ma, C., J. Wei, F. Zhan, R. Wang, K. Fu, X. Wan, et al. 2012. Urinary hypoxia-inducible factor-1 alpha levels are associated with histologic chronicity changes and renal function in patients with lupus nephritis. Yonsei Medical Journal 53: 587–592.CrossRefPubMedPubMedCentral
15.
go back to reference Deng, W., Y. Ren, X. Feng, G. Yao, W. Chen, Y. Sun, et al. 2014. Hypoxia inducible factor-1 alpha promotes mesangial cell proliferation in lupus nephritis. American Journal of Nephrology 40: 507–515.CrossRefPubMed Deng, W., Y. Ren, X. Feng, G. Yao, W. Chen, Y. Sun, et al. 2014. Hypoxia inducible factor-1 alpha promotes mesangial cell proliferation in lupus nephritis. American Journal of Nephrology 40: 507–515.CrossRefPubMed
16.
go back to reference Feng, C.C., Q.L. Ye, Y. Zhu, R.X. Leng, G.M. Chen, J. Yang, et al. 2014. Lack of association between the polymorphisms of hypoxia-inducible factor 1A (HIF1A) gene and SLE susceptibility in a Chinese population. Immunogenetics 66: 9–13.CrossRefPubMed Feng, C.C., Q.L. Ye, Y. Zhu, R.X. Leng, G.M. Chen, J. Yang, et al. 2014. Lack of association between the polymorphisms of hypoxia-inducible factor 1A (HIF1A) gene and SLE susceptibility in a Chinese population. Immunogenetics 66: 9–13.CrossRefPubMed
17.
go back to reference Park, S.Y., S.W. Lee, H.Y. Kim, W.S. Lee, K.W. Hong, and C.D. Kim. 2015. HMGB1 induces angiogenesis in rheumatoid arthritis via HIF-1α activation. European Journal of Immunology 45: 1216–1227.CrossRefPubMed Park, S.Y., S.W. Lee, H.Y. Kim, W.S. Lee, K.W. Hong, and C.D. Kim. 2015. HMGB1 induces angiogenesis in rheumatoid arthritis via HIF-1α activation. European Journal of Immunology 45: 1216–1227.CrossRefPubMed
18.
go back to reference Hu, F., L. Shi, R. Mu, J. Zhu, Y. Li, X. Ma, et al. 2013. Hypoxia-inducible factor-1α and interleukin 33 form a regulatory circuit to perpetuate the inflammation in rheumatoid arthritis. PLoS One 8: e72650.CrossRefPubMedPubMedCentral Hu, F., L. Shi, R. Mu, J. Zhu, Y. Li, X. Ma, et al. 2013. Hypoxia-inducible factor-1α and interleukin 33 form a regulatory circuit to perpetuate the inflammation in rheumatoid arthritis. PLoS One 8: e72650.CrossRefPubMedPubMedCentral
19.
go back to reference Westra, J., E. Brouwer, I.A. van Roosmalen, B. Doornbos-van der Meer, M.A. van Leeuwen, M.D. Posthumus, et al. 2010. Expression and regulation of HIF-1 alpha in macrophages under inflammatory conditions; significant reduction of VEGF by CaMKII inhibitor. BMC Musculoskeletal Disorders 11: 61.CrossRefPubMedPubMedCentral Westra, J., E. Brouwer, I.A. van Roosmalen, B. Doornbos-van der Meer, M.A. van Leeuwen, M.D. Posthumus, et al. 2010. Expression and regulation of HIF-1 alpha in macrophages under inflammatory conditions; significant reduction of VEGF by CaMKII inhibitor. BMC Musculoskeletal Disorders 11: 61.CrossRefPubMedPubMedCentral
20.
go back to reference Brouwer, E., A.S. Gouw, M.D. Posthumus, M.A. van Leeuwen, A.L. Boerboom, J. Bijzet, et al. 2009. Hypoxia inducible factor-1-alpha (HIF-1 alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis. Clinical and Experimental Rheumatology 27: 945–951.PubMed Brouwer, E., A.S. Gouw, M.D. Posthumus, M.A. van Leeuwen, A.L. Boerboom, J. Bijzet, et al. 2009. Hypoxia inducible factor-1-alpha (HIF-1 alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis. Clinical and Experimental Rheumatology 27: 945–951.PubMed
21.
go back to reference Giatromanolaki, A., E. Sivridis, E. Maltezos, N. Athanassou, D. Papazoglou, K.C. Gatter, et al. 2003. Upregulated hypoxia inducible factor-1 alpha and -2 alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Research Therapy 5: R193–R201.CrossRefPubMedPubMedCentral Giatromanolaki, A., E. Sivridis, E. Maltezos, N. Athanassou, D. Papazoglou, K.C. Gatter, et al. 2003. Upregulated hypoxia inducible factor-1 alpha and -2 alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Research Therapy 5: R193–R201.CrossRefPubMedPubMedCentral
22.
go back to reference Hollander, A.P., K.P. Corke, A.J. Freemont, and C.E. Lewis. 2001. Expression of hypoxia-inducible factor 1 alpha by macrophages in the rheumatoid synovium: implications for targeting of therapeutic genes to the inflamed joint. Arthritis Rheumatology 44: 1540–1544.CrossRef Hollander, A.P., K.P. Corke, A.J. Freemont, and C.E. Lewis. 2001. Expression of hypoxia-inducible factor 1 alpha by macrophages in the rheumatoid synovium: implications for targeting of therapeutic genes to the inflamed joint. Arthritis Rheumatology 44: 1540–1544.CrossRef
23.
go back to reference Kunisch, E., S. Chakilam, M. Gandesiri, and R.W. Kinne. 2012. IL-33 regulates TNF-α dependent effects in synovial fibroblasts. International Journal of Molecular Medicine 29: 530–540.PubMedPubMedCentral Kunisch, E., S. Chakilam, M. Gandesiri, and R.W. Kinne. 2012. IL-33 regulates TNF-α dependent effects in synovial fibroblasts. International Journal of Molecular Medicine 29: 530–540.PubMedPubMedCentral
24.
go back to reference del Rey, M.J., E. Izquierdo, S. Caja, A. Usategui, B. Santiago, M. Galindo, et al. 2009. Human inflammatory synovial fibroblasts induce enhanced myeloid cell recruitment and angiogenesis through a hypoxia-inducible transcription factor 1 alpha/vascular endothelial growth factor-mediated pathway in immunodeficient mice. Arthritis Rheumatology 60: 2926–2934.CrossRef del Rey, M.J., E. Izquierdo, S. Caja, A. Usategui, B. Santiago, M. Galindo, et al. 2009. Human inflammatory synovial fibroblasts induce enhanced myeloid cell recruitment and angiogenesis through a hypoxia-inducible transcription factor 1 alpha/vascular endothelial growth factor-mediated pathway in immunodeficient mice. Arthritis Rheumatology 60: 2926–2934.CrossRef
25.
go back to reference Hu, F., R. Mu, J. Zhu, L. Shi, Y. Li, X. Liu, et al. 2014. Hypoxia and hypoxia-inducible factor-1α provoke toll-like receptor signalling- induced inflammation in rheumatoid arthritis. Annals of the Rheumatic Diseases 73: 928–936.CrossRefPubMed Hu, F., R. Mu, J. Zhu, L. Shi, Y. Li, X. Liu, et al. 2014. Hypoxia and hypoxia-inducible factor-1α provoke toll-like receptor signalling- induced inflammation in rheumatoid arthritis. Annals of the Rheumatic Diseases 73: 928–936.CrossRefPubMed
26.
go back to reference Ahn, J.K., E.M. Koh, H.S. Cha, Y.S. Lee, J. Kim, E.K. Bae, et al. 2008. Role of hypoxia-inducible factor-1 alpha in hypoxia-induced expressions of IL-8, MMP-1 and MMP-3 in rheumatoid fibroblast-like synoviocytes. Rheumatology (Oxford) 47: 834–839.CrossRef Ahn, J.K., E.M. Koh, H.S. Cha, Y.S. Lee, J. Kim, E.K. Bae, et al. 2008. Role of hypoxia-inducible factor-1 alpha in hypoxia-induced expressions of IL-8, MMP-1 and MMP-3 in rheumatoid fibroblast-like synoviocytes. Rheumatology (Oxford) 47: 834–839.CrossRef
27.
go back to reference Li, G.F., Y.H. Qin, and P.Q. Du. 2015. Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1α signaling. Life Science 136: 67–72.CrossRef Li, G.F., Y.H. Qin, and P.Q. Du. 2015. Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1α signaling. Life Science 136: 67–72.CrossRef
28.
go back to reference Li, G., Y. Zhang, Y. Qian, H. Zhang, S. Guo, M. Sunagawa, et al. 2013. Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hypoxia by increasing MMP2 and MMP9 expression through NF-κB/HIF-1α pathway. Molecular Immunology 53: 227–236.CrossRefPubMed Li, G., Y. Zhang, Y. Qian, H. Zhang, S. Guo, M. Sunagawa, et al. 2013. Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hypoxia by increasing MMP2 and MMP9 expression through NF-κB/HIF-1α pathway. Molecular Immunology 53: 227–236.CrossRefPubMed
29.
go back to reference Lee, Y.A., H.M. Choi, S.H. Lee, S.J. Hong, H.I. Yang, M.C. Yoo, et al. 2012. Hypoxia differentially affects IL-1β-stimulated MMP-1 and MMP-13 expression of fibroblast-like synoviocytes in an HIF-1α-dependent manner. Rheumatology (Oxford) 1: 443–450.CrossRef Lee, Y.A., H.M. Choi, S.H. Lee, S.J. Hong, H.I. Yang, M.C. Yoo, et al. 2012. Hypoxia differentially affects IL-1β-stimulated MMP-1 and MMP-13 expression of fibroblast-like synoviocytes in an HIF-1α-dependent manner. Rheumatology (Oxford) 1: 443–450.CrossRef
30.
go back to reference Li, G.Q., Y. Zhang, D. Liu, Y.Y. Qian, H. Zhang, S.Y. Guo, et al. 2013. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Molecular and Cellular Biochemistry 372: 221–231.CrossRefPubMed Li, G.Q., Y. Zhang, D. Liu, Y.Y. Qian, H. Zhang, S.Y. Guo, et al. 2013. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Molecular and Cellular Biochemistry 372: 221–231.CrossRefPubMed
31.
32.
go back to reference Knowles, H.J., and N.A. Athanasou. 2009. Acute hypoxia and osteoclast activity: a balance between enhanced resorption and increased apoptosis. Journal of Pathology 218: 256–264.CrossRefPubMed Knowles, H.J., and N.A. Athanasou. 2009. Acute hypoxia and osteoclast activity: a balance between enhanced resorption and increased apoptosis. Journal of Pathology 218: 256–264.CrossRefPubMed
33.
go back to reference Knowles, H.J., A.M. Cleton-Jansen, E. Korsching, and N.A. Athanasou. 2010. Hypoxia-inducible factor regulates osteoclast-mediated bone resorption: role of angiopoietin-like 4. FASEB Journal 24: 4648–4659.CrossRefPubMedPubMedCentral Knowles, H.J., A.M. Cleton-Jansen, E. Korsching, and N.A. Athanasou. 2010. Hypoxia-inducible factor regulates osteoclast-mediated bone resorption: role of angiopoietin-like 4. FASEB Journal 24: 4648–4659.CrossRefPubMedPubMedCentral
Metadata
Title
Hypoxia-Inducible Factor-1α and Autoimmune Lupus, Arthritis
Authors
Zu-Cheng Yang
Yi Liu
Publication date
01-06-2016
Publisher
Springer US
Published in
Inflammation / Issue 3/2016
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-016-0337-z

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