title: Low expression of IL-6 and TNF-α correlates with the presence of the nuclear regulators of NF-κB, IκBNS and BCL-3, in the uterus of mice.
abstract: The dynamic regulation of NF-κB 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-κB transcriptional activity in different tissues are of growing interest. IκBNS and BCL-3 are negative nuclear regulators of NF-κB activity that regulate IL-6 and TNF-α 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-α, and their correspondent negative transcription regulators IκBNS or BCL-3 using real-time PCR, western blot and immunochemistry. We found that the expression of TNF-α and IL-6 was oscillatory along the estrous cycle, and its low expression coincided with the presence of BCL-3 and IκBNS, and vice versa, when the presence of the regulators was subtle, the expression of TNF-α and IL-6 was exacerbated. When we compared the production of TNF-α 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-α, but on the contrary, at estrus the expression of BCL-3 is not detected with TNF-α clearly observable along the tissue; the same phenomenon occur in the analysis of IκBNS and IL-6. With that evidence we suggest that the expression of TNF-α and IL-6 might be regulated through NF-κB nuclear regulators BCL-3 and IκBNS in the uterus of mice as has been demonstrated in other systems.
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Edith
authors.initials: E
authors.lastname: Sierra-Mondragón
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gómez-Chávez
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Martín
authors.initials: M
authors.lastname: Murrieta-Coxca
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Ernesto A
authors.initials: EA
authors.lastname: Vázquez-Sánchez
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Isaí
authors.initials: I
authors.lastname: Martínez-Torres
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Cancino-Díaz
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Rojas-Espinosa
authors.affiliation: Department of Microbiology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Cancino-Díaz
authors.affiliation: Department of Physiology, Biophysics, and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Reyes-Sánchez
authors.affiliation: Department of Physiology, Biophysics, and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rodríguez-Muñóz
authors.affiliation: Department of Immunology, National School of Biological Sciences of the National Polytechnic Institute, Mexico City, Mexico. Electronic address: sandrarodm@yahoo.com.mx.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodríguez-Martínez
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D030762:Estrous Cycle / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D014599:Uterus / Q000276:immunology / Q000378:metabolism*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C000631345:Bcl3 protein, mouse; C454819:Nfkbid protein, mouse; C577686:interleukin-6, mouse
keywords: BCL-3; Estrous; IL-6; IκBNS; NFκB; TNF-α