Induction of tumor necrosis factor alpha (TNF) expression in microglia by the accumulation of a superoxide anion donor in rat cerebral cortex
Main Article Content
Abstract
Previously we reported that endotoxin-dependent induction of tumor necrosis factor alpha (TNFexpression in microglia was significantly suppressed by the superoxide anion scavenger N-acetyl cysteine (NAC), and that microglia induced TNF in response to a superoxide anion donor 3-(4-morpholinyl)sydnonimine (SIN-1) in vitro. Those findings strongly suggested that superoxide anion is associated with the induction of TNF in microglia. However, whether TNF is actually induced in microglia in vivo remains to be determined. In the present study, we confirmed the ability of microglia to induce TNF in vitro and examined the effects of SIN-1 on microglial induction of TNF in vivo. The accumulation of SIN-1 solution in rat cerebral cortex led to the induction of TNF on the ipsilateral, but not the contralateral side. The levels of TNF in the ipsilateral cortex peaked at 6-12 h post-accumulation. Immunohistochemical study revealed that anti-TNF antibody-positive cells in the SIN-1-injected region were mainly anti-ionized Ca 2+ binding adapter molecule-1 (Iba-1) antibody-positive, suggesting that microglia are a major cell type for inducing TNF. On the other hand, interleukin 1beta (IL-1) and IL-6 were not detected in the SIN-1-injected cortex. Together, these results indicate that microglia induced TNF in vivo in response to superoxide anion.
Keywords:
tumor necrosis factor alpha, microglia, superoxide anion, rat brain
Article Details
How to Cite
NAKAJIMA, Kazuyuki; ISHIJIMA, Takashi; KOBAYASHI, Hiroshi.
Induction of tumor necrosis factor alpha (TNF) expression in microglia by the accumulation of a superoxide anion donor in rat cerebral cortex.
Medical Research Archives, [S.l.], v. 7, n. 5, may 2019.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1928>. Date accessed: 24 nov. 2024.
doi: https://doi.org/10.18103/mra.v7i5.1928.
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Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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27. Maccioni RB, Rojo LE, Fernández JA, Kuljis RO. The role of neuroimmunomodulation in Alzheimer's disease. Ann NY Acad Sci. 2009;1153:240-246
28. Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di Nicola M, Onofrj M. Peripheral cytokines profile in Parkinson's disease. Brain Behav Immun. 2009;23:55-63
29. Cannella B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol. 1995;37:424-435
30. Yeung MC, Pulliam L, Lau AS. The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-. AIDS. 1995;9:137-143
31. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW. Cytotoxicity of microglia. Glia. 1993;7:111-118
32. Benveniste EN. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med (Berl). 1997;75:165-173
33. Gregersen R, Lambertsen K, Finsen B. Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 2000;20:53-65
34. Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H, Zaheer S, Iyer SS, Zaheer A. Neuroinflammation induces neurodegeneration. J Neurol Neurosurg Spine. 2016;1(1) 1-15
35. Cacci E, Claasen JH, Kokaia Z. Microglia-derived tumor necrosis factor-a exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res. 2005;80:789-797
36. Chung IY, Benveniste EN. Tumor necrosis factor-a production by astrocytes. Induction by lipopolysaccharide, IFN-g, and IL-1b. J Immunol. 1990;144:2999-3007
37. Kim HM, Shin HY, Lim KH, Ryu ST, Shin TY, Chae HJ, Kim HR, Lyu YS, An NH, Lim KS. Taraxacum officinale inhibits tumor necrosis factor-a production from rat astrocytes. Immunopharmacol Immunotoxicol. 2000;22:519-530
2. Venters HD, Dantzer R, Kelley KW. A new concept in neurodegeneration: TNFis a silencer of survival signals. Trends Neurosci. 2000;23:175-180
3. Zassler B, Weis C, Humpel C. Tumor necrosis factor-a triggers cell death of sensitized potassium chloride-stimulated cholinergic neurons. Brain Res Mol Brain Res. 2003;113:78-85
4. Sedel F, Béchade C, Vyas S, Triller A. Macrophage-derived tumor necrosis factor a, an early developmental signal for motoneuron death. J Neurosci. 2004;24:2236-2246
5. Cueva Vargas JL, Osswald IK, Unsain N, Aurousseau MR, Barker PA, Bowie D, Di Polo A. Soluble tumor necrosis factor a promotes retinal ganglion cell death in glaucoma via calcium-permeable AMPA receptor activation. J Neurosci. 2015;35:12088-12102
6. Prajapati P, Sripada L, Singh K, Bhatelia K, Singh R, Singh R. TNF-α regulates miRNA targeting mitochondrial complex-I and induces cell death in dopaminergic cells.
Biochim Biophys Acta. 2015;1852:451-461
7. Nakajima K, Tohyama Y, Kohsaka S, Kurihara T. Protein kinase C requirement in the activation of p38 mitogen-activated protein kinase, which is linked to the induction of tumor necrosis factor in lipopolysaccharide-stimulated microglia. Neurochem Int. 2004;44:205-214
8. Yoshino Y, Yamamoto S, Kohsaka S, Oshiro S, Nakajima K. Superoxide anion contributes to the induction of tumor necrosis factor alpha (TNFα) through activation of the MKK3/6-p38 MAPK cascade in rat microglia. Brain Res. 2011;1422:1-12
9. Hogg N, Darley-Usmar VM, Wilson MT, Moncada S. Production of hydroxyl radicals from the simultaneous generation of superoxide and nitric oxide. Biochem J. 1992;281:419-424
10. Nakajima K, Graeber MB, Sonoda M, Tohyama Y, Kohsaka S, Kurihara T. In vitro proliferation of axotomized rat facial nucleus-derived activated microglia in an autocrine fashion. J Neurosci Res. 2006;84:348-359
11. Maeda S, Nakajima K, Tohyama Y, Kohsaka S. Characteristic response of astrocytes to plasminogen/plasmin to upregulate transforming growth factor beta 3 (TGFb3) production/secretion through proteinase-activated receptor-1 (PAR-1) and the downstream phosphatidylinositol 3-kinase (PI3K)-Akt/PKB signaling cascade. Brain Res. 2009;1305:1-13
12. Lowry OJ, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265-275
13. Ichimiya T, Yamamoto S, Honda Y, Kikuchi R, Kohsaka S, Nakajima K. Functional down-regulation of axotomized rat facial motoneurons. Brain Res. 2013;1507:35-44
14. Arnett HA, Mason J, Marino M, Suzuki K, Matsushima GK, Ting JP. TNFa promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 2001;4:1116-1122
15. Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-a. Nature. 1987;329:630-632
16. Barna BP, Estes ML, Jacobs BS, Hudson S, Ransohoff RM. Human astrocytes proliferate in response to tumor necrosis factor a. J Neuroimmunol. 1990;30:239-343
17. Aloisi F, Carè A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C. Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1b and tumor necrosis factor-a. J Immunol. 1992;149:2358-2366
18. Panek RB, Lee YJ, Itoh-Lindstrom Y, Ting JP, Benveniste EN. Characterization of astrocyte nuclear proteins involved in IFN-g- and TNF-a-mediated class II MHC gene expression. J Immunol. 1994;153:4555-4564
19. Romero LI, Tatro JB, Field JA, Reichlin S. Roles of IL-1 and TNF-a in endotoxin-induced activation of nitric oxide synthase in cultured rat brain cells. Am J Physiol. 1996;270:R326-332
20. Schwartz M, Solomon A, Lavie V, Ben-Bassat S, Belkin M, Cohen A. Tumor necrosis factor facilitates regeneration of injured central nervous system axons. Brain Res. 1991;545:334-338
21. Neumann H, Schweigreiter R, Yamashita T, Rosenkranz K, Wekerle H, Barde YA. Tumor necrosis factor inhibits neurite outgrowth and branching of hippocampal neurons by a rho-dependent mechanism. J Neurosci. 2002;22:854-862
22. von Zahn J, Möller T, Kettenmann H, Nolte C. Microglial phagocytosis is modulated by pro- and anti-inflammatory cytokines. Neuroreport. 1997;8:3851-3856
23. Buttini M, Appel K, Sauter A, Gebicke-Haerter PJ, Boddeke HW. Expression of tumor necrosis factor after focal cerebral ischaemia in the rat. Neurosci. 1996;71:1-16
24. Medana IM, Hunt NH, Chaudhri G. Tumor necrosis factor- expression in the brain during fatal murine cerebral malaria: evidence for production by microglia and astrocytes. Am J Pathol. 1997;150:1473-1486
25. Uno H, Matsuyama T, Akita H, Nishimura H, Sugita M. Induction of tumor necrosis factor-a in the mouse hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab. 1997;17:491-499
26. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ. Tumor necrosis factor-. A mediator of focal ischemic brain injury. Stroke 1997;28:1233-1244
27. Maccioni RB, Rojo LE, Fernández JA, Kuljis RO. The role of neuroimmunomodulation in Alzheimer's disease. Ann NY Acad Sci. 2009;1153:240-246
28. Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di Nicola M, Onofrj M. Peripheral cytokines profile in Parkinson's disease. Brain Behav Immun. 2009;23:55-63
29. Cannella B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol. 1995;37:424-435
30. Yeung MC, Pulliam L, Lau AS. The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-. AIDS. 1995;9:137-143
31. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW. Cytotoxicity of microglia. Glia. 1993;7:111-118
32. Benveniste EN. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med (Berl). 1997;75:165-173
33. Gregersen R, Lambertsen K, Finsen B. Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 2000;20:53-65
34. Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H, Zaheer S, Iyer SS, Zaheer A. Neuroinflammation induces neurodegeneration. J Neurol Neurosurg Spine. 2016;1(1) 1-15
35. Cacci E, Claasen JH, Kokaia Z. Microglia-derived tumor necrosis factor-a exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res. 2005;80:789-797
36. Chung IY, Benveniste EN. Tumor necrosis factor-a production by astrocytes. Induction by lipopolysaccharide, IFN-g, and IL-1b. J Immunol. 1990;144:2999-3007
37. Kim HM, Shin HY, Lim KH, Ryu ST, Shin TY, Chae HJ, Kim HR, Lyu YS, An NH, Lim KS. Taraxacum officinale inhibits tumor necrosis factor-a production from rat astrocytes. Immunopharmacol Immunotoxicol. 2000;22:519-530