Low expression of IL-6 and TNF-alpha correlates with the presence of the nuclear regulators of NF-kappaB, IkBNS and BCL-3, in the uterus of miceEdith Sierra-Mondragon, Fernando Gomez-Chavez, Martin Murrieta-Coxca, ^z>Ernesto A. Vazquez-Sanchez, Isai Martinez-Torres, Mario E. Cancino-Diaz, Oscar Rojas-Espinosa, Juan Carlos Cancino-Diaz, Jose Luis Reyes-Sanchez, Rafael Rodriguez-Munoz, Sandra Rodriguez-Martinez

摘要

The dynamic regulation of NF-kappaB activity in the uterus maintains a favorable environment of cytokines necessary to prepare for pregnancy throughout the estrous cycle. Recently, the mechanisms that directly regulate the NF-kappaB transcriptional activity in different tissues are of growing interest. IkappaBNS and BCL-3 are negative nuclear regulators of NF-kappaB activity that regulate IL-6 and TNF-alpha transcription, respectively. Both cytokines have been described as important factors in the remodeling of uterus for blastocyst implantation. In this work we analyzed in ICR mice the mRNA expression and protein production profile of IL-6, TNF-alpha, and their correspondent negative transcription regulators IkappaBNS or BCL-3 using real-time PCR, western blot and immunochemistry. We found that the expression of TNF-alpha and IL-6 was oscillatory along the estrous cycle, and its low expression coincided with the presence of BCL-3 and IkBNS, and vice versa, when the presence of the regulators was subtle, the expression of TNF-alpha and IL-6 was exacerbated. When we compared the production of TNF-alpha and IL-6 in the different estrous stages relating with diestrus we found that at estrus there is an important increase of the cytokines (p < 0.05) decreasing at metestrus to reach the basal expression at diestrus. In the immunochemistry analysis we found that at diestrus BCL-3 is distributed all over the tissue with a barely detected TNF-alpha, but on the contrary, at estrus the expression of BCL-3 is not detected with TNF-alpha clearly observable along the tissue; the same phenomenon occur in the analysis of IkappaBNS and IL-6. With that evidence we suggest that the expression of TNF-alpha and IL-6 might be regulated through NF-kappaB nuclear regulators BCL-3 and IkBNS in the uterus of mice as has been demonstrated in other systems.