Abstract
In murine bone-marrow stromal microenvironment cells and in human multipotent mesenchymal stromal cells (MMSCs), proinflammatory cytokine interleukin-1 beta (IL-1β) serves as a growth factor. In murine bone tissue, IL-1β expression increases in vivo after irradiation. Here, we have presented our evaluation of the effects of exogenous IL-1β on the expression of NF-kB transcription factors in human MMSCs and stromal layer cells of murine long-term bone marrow cultures (LTBMCs). The cytokine signaling pathway was also activated in murine LTBMC by braking electron radiation in doses of 3–12 Gy. The level of expression of genes that code for IL-1β, IL-1β type-I receptor and NF-kB and IKK protein families have been studied at different time points post exposure. In both human and murine stromal cells, exogenous IL-1β led to an increase in the level of expression of its own gene, while levels of expression of NF-kB and IKK gene families were not substantially changed. Nevertheless, in human cells, a significant correlation between levels of expression of IL-1β and all NF-kB family genes was detected. It points to a similarity in IL-1β signal pathways in mesenchymal and hematopoietic cells, where the posttranslational modifications of NF-kB transcription factors play a major role. The irradiation of murine LTBMC resulted in a transient increase in the expression of genes that code NF-kB transcription factors and IL-1β. These results indicate an important role of Rel, Rela, Relb, and Nfkb2 genes in the induction of IL-1β signal pathway in murine stromal cells. An increase in IL-1β expression after the irradiation of stromal cells may be related to both the induction of inflammation due to massive cell death and to a profound stimulation of the expression of this proinflammatory cytokine expression.
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Abbreviations
- LTBMC:
-
long-term bone-marrow culture of Dexter type
- IL-1β:
-
interleukin-1 beta
- MMSC:
-
multipotent mesenchymal stromal cell
References
Dinarello C.A. 1996. Biologic basis for interleukin-1 in disease. Blood. 87, 2095–2147.
Dinarello C.A. 2011. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 117, 3720–3732.
Schmidt J.A., Mizel S.B., Cohen D., Green I. 1982. Interleukin 1, a potential regulator of fibroblast proliferation. J. Immunol. 128, 2177–2182.
Taichman R.S. 2005. Blood and bone: Two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood. 105, 2631–2639.
Glossop J.R., Cartmell S.H. 2009. Effect of fluid flowinduced shear stress on human mesenchymal stem cells: Differential gene expression of IL1B and MAP3K8 in MAPK signaling. Gene Exp. Patterns. 9, 381–388.
Bigildeev A.E., Zezina E.A., Shipounova I.N., Drize N.J. 2015. Interleukin-1 beta enhances human multipotent mesenchymal stromal cell proliferative potential and their ability to maintain hematopoietic precursor cells. Cytokine. 71, 246–254.
Bigildeev A.E., Zhironkina O.A., Lubkova O.N., Drize N.J. 2013. Interleukin-1 beta is an irradiationinduced stromal growth factor. Cytokine. 64, 131–137.
Weber A., Wasiliew P., Kracht M. 2010. Interleukin-1 (IL-1) pathway. Sci. Signal. 3 (105), cm1. doi 10.1126/ scisignal.3105cm1
Hayden M.S., Ghosh S. 2004. Signaling to NF-kappaB. Genes Dev. 18, 2195–2224.
Bonizzi G., Karin M. 2004. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 25, 280–288.
Karin M., Ben-Neriah Y. 2000. Phosphorylation meets ubiquitination: The control of NF-[kappa]B activity. Annu Rev. Immunol. 18, 621–663.
Ten R.M., Paya C.V., Israël N., Le Bail O., Mattei M.G., Virelizier J.L., Kourilsky P., Israël A. 1992. The characterization of the promoter of the gene encoding the p50 subunit of NF-kappa B indicates that it participates in its own regulation. EMBO J. 11, 195–203.
Lombardi L., Ciana P., Cappellini C., Trecca D., Gueminil L., Migliazza A., Malolo A.T., Neri A., Spermentale E., Ematologia S., Scienze I., Irccs O.M. 1995. Structural and functional characterization of the promoter regions of the NFKB2 gene. Nucleic Acids Res. 23, 2328–2336.
Hannink M., Temin H.M. 1990. Structure and autoregulation of the c-rel promoter. Oncogene. 5, 1843–1850.
Svinareva D.A., Shipunova I.N., Olshanskaya Yu.V., Momotyuk K.S., Drize N.I. 2010. Basic properties of mesenchymal stromal cells from the donot bone marrow: Surface markers. Terapevt. Artkhiv. 6, 52–57.
Chomczynski P., Sacchi N. 2006. The single-step method of RNA isolation by acid guanidinium thiocyanate- phenol-chloroform extraction: Twenty-something years on. Nat. Protoc. 1, 581–585.
Vandesompele J., De Preter K., Pattyn F., Poppe B., Van Roy N., De Paepe A., Speleman F. 2002. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, RESEARCH0034.
Schmittgen T.D., Livak K.J. 2008. Analyzing real-time PCR data by the comparative CT method. Nat. Protoc. 3, 1101–1108.
Bigil’deev A.E., Zezina E.A., Shipunova I.N., Drize N.I. 2014. Effect of interleutin-1beta on multipotent mesenchymal stromal cells: Proliferation, differentiation, and the ability to maintain hematopoietic stem cells. In: Stvolovye kletki i regenerativnaya meditsina (Stem Cells and Regenerative Medicine), Moscow: Mosk. Gos. Univ., pp. 22–39.
Linard C., Ropenga A., Vozenin-Brotons M.C., Chapel A., Mathe D. 2003. Abdominal irradiation increases inflammatory cytokine expression and activates NF-kappaB in rat ileal muscularis layer. Am. J. Physiol. Gastrointest. Liver Physiol. 285, G556–G565.
Linard C., Marquette C., Mathieu J., Pennequin A., Clarençon D., Mathé D. 2004. Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: Effect of an NF-kappaB inhibitor. Int. J. Radiat. Oncol. Biol. Phys. 58, 427–434.
Johnston C.J., Piedboeuf B., Rubin P., Williams J.P., Baggs R., Finkelstein J.N. 1996. Early and persistent alterations in the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor alpha mRNA levels in fibrosis-resistant and sensitive mice after thoracic irradiation. Radiat. Res. 145, 762–767.
Zhou D., Yu T., Chen G., Brown S.A., Yu Z., Mattson M.P., Thompson J.S. 2001. Effects of NF-kappaB1 (p50) targeted gene disruption on ionizing radiation-induced NF-kappaB activation and TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in vivo. Int. J. Radiat. Biol. 77, 763–772.
Chertkov J.L., Gurevitch O.A. 1984. Hematopoietic Stem Cell and Its Microenvironment. Moscow: Meditsina.
Matsumoto H., Takahashi A., Ohnishi T. 2004. Radiation- induced adaptive responses and bystander effects. Uchū Seibutsu Kagaku. 18, 247–254.
DiDonato J.A., Mercurio F., Karin M. 1995. Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B.Mol. Cell Biol. 15, 1302–1311.
Carrero R., Cerrada I., Lledó E., Dopazo J., García-García F., Rubio M.-P., Trigueros C., Dorronsoro A., Ruiz-Sauri A., Montero J.A., Sepúlveda P. 2012. IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB. Stem. Cell Rev. 8, 905–916.
Macaeva E., Saeys Y., Tabury K., Janssen A., Michaux A., Benotmane M.A., De Vos W.H., Baatout S., Quintens R. 2016. Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry. Sci. Rep. 6, 19251.
Warters R.L., Packard A.T., Kramer G.F., Gaffney D.K., Moos P.J. 2009. Differential gene expression in primary human skin keratinocytes and fibroblasts in response to ionizing radiation. Radiat. Res. 172, 82–95.
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Original Russian Text © A.E. Bigildeev, E.A. Zezina, N.J. Drize, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 3, pp. 447–459.
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Bigildeev, A.E., Zezina, E.A. & Drize, N.J. The effects of interleukin-1 beta and gamma-quantum braking radiation on mesenchymal progenitor cells. Mol Biol 51, 393–403 (2017). https://doi.org/10.1134/S0026893317020054
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DOI: https://doi.org/10.1134/S0026893317020054