Features of the Expression of NF-kB Pathway Genes in Tissues of Irradiated Mice and in Old Animals

Abstract

Abstract—The transcription factors of NF-kB family match the external signal from pro-inflammatory cytokines and transcription of their target genes. It was previously shown that in the peripheral blood of irradiated young and nonirradiated old mice, an increased level of interleukin-1β is maintained, which is simultaneously the activator and the target gene of NF-kB signaling pathway. We suggested that during both induced by radiation and natural aging, similar processes can take place in various tissues of the body, accompanied by the activation of NF-kB. To test this hypothesis and establish the characteristics of induced and natural aging, we studied the expression of NF-kB family genes, its IKK regulatory complex and NF-kB target genes at the level of transcription in bone marrow, spleen, thymus, liver and muscles of irradiated mice three months after exposure and in the same tissues of old mice. RNA was extracted from the tissues, reverse transcription was performed followed by real-time PCR. It was shown that, in general, the pattern of changes in the expression of NF-kB differs in irradiated and old animals and, moreover, depends on the type of tissue. Biochemical processes occurring during natural and accelerated radiation aging affect NF-kB signaling pathway, but the details of its activation differ from each other under these conditions. However, general trends were identified. In the bone marrow, common for irradiation and aging was a reduction in the expression of Nemo encoding the subunit of the regulatory IKK complex NF-kB. In the thymus, common feature for these conditions was a decrease in Ikkb expression, which encodes another subunit of the same IKK complex. This indicates an important role of these genes in maintaining normal functioning of hematopoietic tissue. In older mice, expression of the gene encoding IL-1β was increased in the thymus, spleen, and liver. The production of IL-1β by these tissues may contribute to an increase in its concentration in peripheral blood.