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Expression of mRNAs for IL-1β, IL-6, IL-10, TNFα, CX3CL1, and TGFβ1 Cytokines in the Brain Tissues: Assessment of Contribution of Blood Cells with and without Perfusion

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Abstract

Cytokines are important regulators of brain function under both normal and pathological conditions. Cytokines can be synthesized by resident cells of the central nervous system (CNS) (vascular endothelium, cells of the blood-brain barrier, parenchymal cells of the CNS) or cells in the lumen of blood vessels, as well as introduced with the bloodstream. The ratio between the quantity of cytokines synthesized in the CNS and those entering it from external sources under various conditions remains poorly understood. In this work, we studied the contribution of mRNAs from non-resident cells to the common pool of cytokine (TNFα, IL-1β, IL-6, IL-10, CX3CL1, and TGFβ1) mRNAs in the rat neocortex, hippocampus, dura matter, pia matter, and choroid plexus. We also evaluated the representation of various populations of resident and non-resident immune cells based on the expression of marker genes (Ncf1, Tbx21, Foxp3, RORγc). The removal of blood by transcardial perfusion led to a decrease in the quantity of the TNFα mRNA in the neocortex and hippocampus and of the IL-1β, IL-6, and IL-10 mRNAs in the dura mater. The mRNA levels of other cytokines in studied structures were not affected by perfusion. Our findings suggest that mRNAs present in the blood can make a significant contribution to the mRNA levels of some cytokines in the CNS; therefore, preliminary perfusion of brain tissue is a necessary stage of experimental design for correct estimation of mRNA content in the brain.

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Abbreviations

CX3CL1:

C-X3-C chemokine ligand 1 (fractalkine)

IL:

interleukin

TNFα:

tumor necrosis factor alpha

TGFβ1:

transforming growth factor beta 1

References

  1. Estes, M. L., and McAllister, A. K. (2014) Alterations in immune cells and mediators in the brain: it’s not always neuroinflammation! Brain Pathol., 24, 623–630, doi: https://doi.org/10.1111/bpa.12198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zeisel, A., Munoz-Manchado, A. B., Codeluppi, S., Lonnerberg, P., La Manno, G., Jureus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., Rolny, C., Castelo-Branco, G., Hjerling-Leffler, J., and Linnarsson, S. (2015) Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq, Science, 347, 1138–1142, doi: https://doi.org/10.1126/science.aaa1934.

    Article  CAS  PubMed  Google Scholar 

  3. Meyer, U., Murray, P. J., Urwyler, A., Yee, B. K., Schedlowski, M., and Feldon, J. (2008) Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling, Mol. Psychiatry, 13, 208–221, doi: 10.1038/sj.mp.4002042.

  4. Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O’Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., Deng, S., Liddelow, S. A., Zhang, C., Daneman, R., Maniatis, T., Barres, B. A., and Wu, J. Q. (2014) An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex, J. Neurosci., 34, 11929–11947, doi: https://doi.org/10.1523/JNEUROSCI.1860-14.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pisanu, A., Lecca, D., Mulas, G., Wardas, J., Simbula, G., Spiga, S., and Carta, A. R. (2014) Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR-γ agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson’s disease, Neurobiol. Dis., 71, 280–291, doi: https://doi.org/10.1016/j.nbd.2014.08.011.

    Article  CAS  PubMed  Google Scholar 

  6. Rogers, J. T., Morganti, J. M., Bachstetter, A. D., Hudson, C. E., Peters, M. M., Grimmig, B. A., Weeber, E. J., Bickford, P. C., and Gemma, C. (2011) CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity, J. Neurosci., 31, 16241–16250, doi: https://doi.org/10.1523/JNEUROSCI.3667-11.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Louveau, A., Herz, J., Alme, M. N., Salvador, A. F., Dong, M. Q., Viar, K. E., Herod, S. G., Knopp, J., Setliff, J. C., Lupi, A. L., Da Mesquita, S., Frost, E. L., Gaultier, A., Harris, T. H., Cao, R., Hu, S., Lukens, J. R., Smirnov, I., Overall, C. C., Oliver, G., and Kipnis, J. (2018) CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature, Nat. Neurosci., 21, 1380–1391, doi: https://doi.org/10.1038/s41593-018-0227-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Filiano, A. J., Gadani, S. P., and Kipnis, J. (2017) How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat. Rev. Neurosci., 18, 375–384, doi: https://doi.org/10.1038/nrn.2017.39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Marques, F., and Sousa, J. C. (2015) The choroid plexus is modulated by various peripheral stimuli: implications to diseases of the central nervous system, Front. Cell. Neurosci., 9, 136, doi: https://doi.org/10.3389/fncel.2015.00136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ding, X., Zhang, M., Gu, R., Xu, G., and Wu, H. (2017) Activated microglia induce the production of reactive oxygen species and promote apoptosis of co-cultured retinal microvascular pericytes, Graefe’s Arch. Clin. Exp. Ophthalmol., 255, 777–788, doi: https://doi.org/10.3389/fncel.2015.00136.

    Article  CAS  Google Scholar 

  11. Ferreira, L., Hamey, F., Teichmann, S. A., Cvejic, A., Macaulay, I. C., Svensson, V., Labalette, C., and Voet, T. (2016) Single-cell RNA-sequencing reveals a continuous spectrum of differentiation in hematopoietic cells, Cell Rep., 14, 966–977, doi: https://doi.org/10.1016/j.celrep.2015.12.082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Prieto Martin, P., Bending, D., Ono, M., Ducker, C. B., Crompton, T., and Paduraru, A. (2018) A temporally dynamic Foxp3 autoregulatory transcriptional circuit controls the effector Treg programme, EMBO J., 37, e99013, doi: https://doi.org/10.15252/embj.201899013.

    PubMed  PubMed Central  Google Scholar 

  13. Zhao, Y., Balato, A., Fishelevich, R., Chapoval, A., Mann, D. L., and Gaspari, A. A. (2009) Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis, Br. J. Dermatol., 161, 1301–1306, doi: https://doi.org/10.1111/j.1365-2133.2009.09400.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dobryakova, Y. V., Kasianov, A., Zaichenko, M. I., Stepanichev, M. Y., Chesnokova, E. A., Kolosov, P. M., Markevich, V. A., and Bolshakov, A. P. (2018) Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus, Front. Mol. Neurosci., 10, doi: https://doi.org/10.3389/fnmol.2017.00429.

  15. Williams, A., Zandee, S. E. J., Mair, I., Anderton, S. M., O’Connor, R. A., and Leech, M. D. (2017) IL-10-producing, ST2-expressing Foxp3+ T-cells in multiple sclerosis brain lesions, Immunol. Cell Biol., 95, 484–490, doi: https://doi.org/10.1038/icb.2017.3.

    Article  CAS  PubMed  Google Scholar 

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Funding

Funding. This work was supported by the Russian Foundation for Basic Research (project 18-015-00314a).

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Correspondence to N. V. Gulyaeva.

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Conflict of interest. The authors declare no conflict of interest.

Ethical approval. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The experimental protocol was approved by the Ethics Committee of the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences.

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Published in Russian in Biokhimiya, 2019, Vol. 84, No. 8, pp. 1147–1153.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19–086, June 10, 2019.

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Kvichansky, A.A., Volobueva, M.N., Spivak, Y.S. et al. Expression of mRNAs for IL-1β, IL-6, IL-10, TNFα, CX3CL1, and TGFβ1 Cytokines in the Brain Tissues: Assessment of Contribution of Blood Cells with and without Perfusion. Biochemistry Moscow 84, 905–910 (2019). https://doi.org/10.1134/S0006297919080066

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