The talented interferon-gamma

Abstract

IFN-γ is an extraordinarily pleotropic cytokine. It can not only heighten both the innate and adaptive immune response against pathogens and tumors, but also has the ability to maintain immune homeostasis. Since the effects of IFN-γ are cell and tissue specific, it is important to consider the recent advances in IFN-γ signaling in the context of different diseases. To this end, we review the involvement of IFN-γ in the pathogenesis of several inflammatory diseases, its therapeutic potential as an anti-tumor agent and its effects upon stem cells.

Share and Cite:

Lin, F. and Young, H. (2013) The talented interferon-gamma. Advances in Bioscience and Biotechnology, 4, 6-13. doi: 10.4236/abb.2013.47A3002.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Lin, F.-C. and Young, H. (2012) Interferon-gamma, in encyclopedia of signaling molecules. Springer, New York, 966-972.
[2] Tabas, I., Williams, K.J. and Boren, J. (2007) Subendothelial lipoprotein retention as the initiating process in atherosclerosis: Update and therapeutic implications. Circulation, 116, 1832-1844. doi:10.1161/CIRCULATIONAHA.106.676890
[3] Hao, X.R., et al. (2009) IFN-gamma down-regulates ABCA1 expression by inhibiting LXRalpha in a JAK/ STAT signaling pathway-dependent manner. Atherosclerosis, 203, 417-428. doi:10.1016/j.atherosclerosis.2008.07.029
[4] Li, N., et al. (2010) ERK is integral to the IFN-gammamediated activation of STAT1, the expression of key genes implicated in atherosclerosis, and the uptake of modified lipoproteins by human macrophages. The Journal of Immunology, 185, 3041-3048. doi:10.4049/jimmunol.1000993
[5] Ahmad, U., et al. (2010) IFN-gamma primes intact human coronary arteries and cultured coronary smooth muscle cells to double-stranded RNAand self-RNAinduced inflammatory responses by upregulating TLR3 and melanoma differentiation-associated gene 5. The Journal of Immunology, 185, 1283-1294. doi:10.4049/jimmunol.0902283
[6] Bergstrom, I., et al. (2012) Persistent accumulation of interferon-gamma-producing CD8+CD56+ T cells in blood from patients with coronary artery disease. Atherosclerosis, 224, 515-520. doi:10.1016/j.atherosclerosis.2012.07.033
[7] Kim, K., et al. (2011) Replicated association of a regulatory polymorphism in the interferon gamma gene with lupus susceptibility. Annals of the Rheumatic Diseases, 70, 1878-1879. doi:10.1136/ard.2010.147249
[8] Harigai, M., et al. (2008) Excessive production of IFNgamma in patients with systemic lupus erythematosus and its contribution to induction of B lymphocyte stimulator/B cell-activating factor/TNF ligand super-family-13B. The Journal of Immunology, 181, 2211-2219.
[9] Karonitsch, T., et al. (2009) Activation of the interferongamma signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells. Arthritis & Rheumatism, 60, 1463-1471. doi:10.1002/art.24449
[10] Lee, S.K., et al. (2012) Interferon-gamma excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity, 37, 880-892. doi:10.1016/j.immuni.2012.10.010
[11] Lee, E., et al. (2012) IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci. Journal of Neuroinflammation, 9, 7.
[12] Hindinger, C., et al. (2012) IFN-gamma signaling to astrocytes protects from autoimmune mediated neurological disability. PLoS One, 7, e42088. doi:10.1371/journal.pone.0042088
[13] Lees, J.R. and Cross, A.H. (2007) A little stress is good: IFN-gamma, demyelination, and multiple sclerosis. Journal of Clinical Investigation, 117, 297-299. doi:10.1172/JCI31254
[14] Schurgers, E., Billiau, A. and Matthys, P. (2011) Collagen-induced arthritis as an animal model for rheumatoid arthritis: focus on interferon-gamma. Journal of Interferon & Cytokine Research, 31, 917-926. doi:10.1089/jir.2011.0056
[15] Page, C.E., et al. (2010) Interferon-gamma inhibits interleukin-1beta-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis. Arthritis Research & Therapy, 12, R49.
[16] Karonitsch, T., et al. (2012) Interferon signals and monocytic sensitization of the interferon-gamma signaling pathway in the peripheral blood of patients with rheumatoid arthritis. Arthritis & Rheumatism, 64, 400-408. doi:10.1002/art.33347
[17] Doodes, P.D., et al. (2010) IFN-gamma regulates the requirement for IL-17 in proteoglycan-induced arthritis. The Journal of Immunology, 184, 1552-1559. doi:10.4049/jimmunol.0902907
[18] Saha, B., et al. (2009) Gene modulation and immunoregulatory roles of interferon gamma. Cytokine, 50, 1-14. doi:10.1016/j.cyto.2009.11.021
[19] Lipnik, K., et al. (2010) Interferon gamma-induced human guanylate binding protein 1 inhibits mammary tumor growth in mice. Molecular Medicine, 16, 177-187.
[20] Li, P., et al. (2012) Interferon-gamma induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF-1). Cancer Letters, 314, 213-222. doi:10.1016/j.canlet.2011.09.031
[21] Schmitt, M.J., et al. (2012) Interferon-gamma-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells. Cell Communication and Signaling, 10, 41.
[22] Tate, D.J., et al. (2012) Interferon-gamma-induced nitric oxide inhibits the proliferation of murine renal cell carcinoma cells. International Journal of Biological Sciences, 8, 1109-1120. doi:10.7150/ijbs.4694
[23] Mi, Y.Y., et al. (2011) Interferon gamma +874 T/A polymorphism contributes to cancer susceptibility: A meta-analysis based on 17 case-control studies. Molecular Biology Reports, 38, 4461-4467. doi:10.1007/s11033-010-0575-3
[24] Syu, L.J., et al. (2012) Transgenic expression of interferon-gamma in mouse stomach leads to inflammation, metaplasia, and dysplasia. American Journal of Pathology, 181, 2114-2125. doi:10.1016/j.ajpath.2012.08.017
[25] Zaidi, M.R., et al. (2011) Interferon-gamma links ultraviolet radiation to melanomagenesis in mice. Nature, 469, 548-553. doi:10.1038/nature09666
[26] Berthon, C., et al. (2010) In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors. Cancer Immunology, Immunotherapy, 59, 1839-1849. doi:10.1007/s00262-010-0909-y
[27] Chen, J., et al. (2012) Interferon-gamma-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology, 217, 385-393. doi:10.1016/j.imbio.2011.10.016
[28] Marsal, J. and Agace, W.W. (2012) Targeting T-cell migration in inflammatory bowel disease. Journal of Internal Medicine, 272, 411-429. doi:10.1111/j.1365-2796.2012.02588.x
[29] Nava, P., et al. (2010) Interferon-gamma regulates intestinal epithelial homeostasis through converging betacatenin signaling pathways. Immunity, 32, 392-402. doi:10.1016/j.immuni.2010.03.001
[30] Capaldo, C.T., et al. (2012) IFN-gamma and TNF-alphainduced GBP-1 inhibits epithelial cell proliferation through suppression of beta-catenin/TCF signaling. Mucosal Immunology, 5, 681-690. doi:10.1038/mi.2012.41
[31] Colgan, S.P. and Taylor, C.T. (2010) Hypoxia: An alarm signal during intestinal inflammation. Nature Reviews Gastroenterology & Hepatology, 7, 281-287. doi:10.1038/nrgastro.2010.39
[32] Glover, L.E., et al. (2011) IFN-gamma attenuates hypoxia-inducible factor (HIF) activity in intestinal epithetlial cells through transcriptional repression of HIF-1beta. The Journal of Immunology, 186, 1790-1798. doi:10.4049/jimmunol.1001442
[33] Ahern, P.P., et al. (2010) Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity, 33, 279-288. doi:10.1016/j.immuni.2010.08.010
[34] Sheikh, S.Z., et al. (2010) Cutting edge: IFN-gamma is a negative regulator of IL-23 in murine macrophages and experimental colitis. The Journal of Immunology, 184, 4069-4073. doi:10.4049/jimmunol.0903600
[35] Jin, Y., et al. (2012) IL-17/IFN-gamma interactions regulate intestinal inflammation in TNBS-induced acute colitis. Journal of Interferon & Cytokine Research, 32, 548-556. doi:10.1089/jir.2012.0030
[36] Ito, R., et al. (2006) Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice. Clinical & Experimental Immunology, 146, 330338. doi:10.1111/j.1365-2249.2006.03214.x
[37] Glass, C.K., et al. (2010) Mechanisms underlying inflammation in neurodegeneration. Cell, 140, 918-934. doi:10.1016/j.cell.2010.02.016
[38] Jung, J.S., Kim, D.H. and Kim, H.S. (2010) Ginsenoside Rh1 suppressesinducible nitric oxide synthase gene expression in IFN-gamma-stimulated microglia via modulation of JAK/STAT and ERK signaling pathways. Biochemical and Biophysical Research Communications, 397, 323-328. doi:10.1016/j.bbrc.2010.05.117
[39] Chakrabarty, P., et al. (2011) Interferon-gamma induces progressive nigrostriatal degeneration and basal ganglia calcification. Nature Neuroscience, 14, 694-696.
[40] Barcia, C., et al. (2012) IFN-gamma signaling, with the synergistic contribution of TNF-alpha, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s disease. Cell Death & Disease, 2, e142.
[41] Browne, T.C., et al. (2013) IFN-gamma production by amyloid beta-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer’s disease. The Journal of Immunology, 190, 2241-2251. doi:10.4049/jimmunol.1200947
[42] Ryu, H.J., et al. (2010) The protective effects of interleukin-18 and interferon-gamma on neuronal damages in the rat hippocampus following status epilepticus. Neuroscience, 170, 711-721. doi:10.1016/j.neuroscience.2010.07.048
[43] Victorio, S.C., Havton, L.A. and Oliveira, A.L. (2010) Absence of IFNgamma expression induces neuronal degeneration in the spinal cord of adult mice. Journal of Neuroinflammation, 7, 77.
[44] Chakrabarty, P., et al. (2010) IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice. The Journal of Immunology, 184, 5333-5343. doi:10.4049/jimmunol.0903382
[45] De Bruin, A.M., et al. (2013) Interferon-gamma impairs proliferation of hematopoietic stem cells in mice. Blood, 121, 3578-3585. doi:10.1182/blood-2012-05-432906
[46] Baldridge, M.T., et al. (2010) Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature, 465, 793-797.
[47] MacNamara, K.C., et al. (2011) Infection-induced myelopoiesis during intracellular bacterial infection is critically dependent upon IFN-gamma signaling. The Journal of Immunology, 186, 1032-1043. doi:10.4049/jimmunol.1001893
[48] Zahir, T., et al. (2009) Neural stem/progenitor cells differentiate in vitro to neurons by the combined action of dibutyryl cAMP and interferon-gamma. Stem Cells and Development, 18, 1423-1432. doi:10.1089/scd.2008.0412
[49] Tanner, D.C., Cherry, J.D. and Mayer-Proschel, M. (2011) Oligodendrocyte progenitors reversibly exit the cell cycle and give rise to astrocytes in response to interferongamma. The Journal of Neuroscience, 31, 6235-6246. doi:10.1523/JNEUROSCI.5905-10.2011
[50] Duque, G., et al. (2009) Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role in early osteoblastogenesis. Stem Cells, 27, 550-558. doi:10.1634/stemcells.2008-0886

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.