Changes in expression of nuclear factor kappa B subunits in the ovine thymus during early pregnancy

Abstract

There is a pregnant maternal immunological tolerance that protects the fetus and promotes its growth, and nuclear factor kappa B (NF-κB) family participates in the regulation of innate immune and adaptive immune responses. The thymus is related to establishing central tolerance, and early pregnancy has effects on expression of a good number of genes and proteins in the maternal thymus in sheep. However, it is unclear whether early pregnancy changes expression of NF-κB subunits in the ovine thymus. In this study, the thymic samples were collected from day 16 of non-pregnant ewes, and days 13, 16 and 25 of pregnant ewes, and the expression of NF-κB members (NF-κB1, NF-κB2, RelA, RelB and c-Rel) was analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis. The results showed that c-Rel mRNA and protein upregulated at day 25 of pregnancy, and NF-κB1 mRNA and proteins increased at days 16 and 25 of pregnancy, and RelB mRNA and proteins enhanced during early pregnancy. However, expression levels of NF-κB2 and RelA were decreased during early pregnancy, but upregulated from day 13 to 25 of pregnancy. In addition, the RelA protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. This paper reported for the first time that early pregnancy induced expression of NF-κB1, RelB and c-Rel, but inhibited expression of NF-κB2 and RelA in the maternal thymus during early pregnancy, which is involved in the central immune tolerance, and helpful for successful pregnancy in sheep.

Regulation of IkappaB Protein Expression by Early Gestation in the Thymus of Ewes

“…As a type I interferon, IFNT has effects on the ovine maternal thymus to stimulate ISG15 expression, and progesterone affects thymic immune functions by modulating the progesterone-induced blocking factor expression via the progesterone receptor [ 62 ]. Early pregnancy affects the expression of the NF-κB family and improves NF-κB1, RelB, and c-Rel expression but suppresses NF-κB2 and RelA expression in the thymus of ewes [ 63 ]. NF-κB is important for thymic T-cell maturation and proliferation, and type I IFN can improve T-cells’ response to inflammatory factors in the thymic medulla [ 64 ].…”

Expression of IkappaB Family in the Ovine Liver during Early Pregnancy

“…NF-κB regulates over 400 genes related to inflammation, apoptosis and angiogenesis that are associated with maternal immunosuppression and maintaining gestation. Furthermore, the expression of NF-κB components, including NF-κB p105, NF-κB p100, p65, RelB and c-Rel, is changed in the maternal immune organs in ewes, which are related to the maternal immunoregulation, embryo implantation and pregnancy maintenance in sheep [ 26 , 27 , 28 , 29 ]. Inhibitors of the NF-κB (IκB) family include IκBα, IκBβ, IκBε, IKKγ, B cell leukemia-3 (BCL-3), IκBNS (also known as NFKBID) and IκBζ, which participate in the regulation of innate immune responses [ 30 ].…”

Early Pregnancy Regulates Expression of IkappaB Family in Ovine Spleen and Lymph Nodes

“…Nuclear factor kappa B (NF-κB) is implicated in both physiological and pathological processes; NF-κB regulation is essential during pregnancy, and dysregulation results in premature termination of pregnancy, with bad outcomes for the mother and the fetus [ 5 ]. Early pregnancy modulates the expression of NF-κB components in the maternal thymus, spleen, liver and inguinal lymph nodes, which is necessary for embryo implantation and pregnancy maintenance in sheep [ 6 , 7 , 8 , 9 ].…”