title: Impact of C-rel inhibition of cord blood-derived B-, T-, and NK cells.
abstract: The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells. This particular source was selected as cord blood is an important source of cells used for transplantation and immunotherapy, primarily in treating leukemias. As stem cell factor (SCF) and FLT3 are important agents for hematopoietic stem cell expansion, and cytokines like interleukin (IL)-2, -7, and -15 are essential for T- and B- (and also NK) cell development and proliferation, the current study evaluated c-Rel expression in cord blood mononuclear cells and CD34+cells, as well as effects on B-, T-, and NK cells associated with alterations in c-Rel expression, using flow cytometry and PCR. The results showed c-Rel expression increased among cells cultured in the presence of SCF and FLT3 but was reduced when IL-2, IL-7, and IL-15 were used all together. Further, inhibition of c-Rel expression by siRNA reduced cord blood-derived B-, T-, and NK cell differentiation and expansion. These results indicated that with cells isolated from cord blood, c-Rel has an important role in B-, T-, and NK cell differentiation and, further, that agents (select cytokines/growth factors) that could impact on its expression might not only affect immune cell profiles in a host but could potentially also limit apoptotic activities in (non-)immune cells in that host. In the context of cancer (immuno)therapy, in particular, when cord blood is used an important source in stem cell transplantation in leukemia patients, such down-regulating changes in c-Rel levels could be counter-productive.
authors.affiliation: a Stem Cell Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|b Student Research Committee, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Fallahi
authors.affiliation: a Stem Cell Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|b Student Research Committee, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Seyede Momeneh
authors.initials: SM
authors.lastname: Mohammadi
authors.affiliation: c Tissue Engineering Research Group , Advanced Research School, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Tayefi Nasrabadi
authors.affiliation: c Tissue Engineering Research Group , Advanced Research School, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Alihemmati
authors.affiliation: d Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Samadi
authors.affiliation: a Stem Cell Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.|b Student Research Committee, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Gholami
authors.affiliation: e Immunology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Shanehbandi
authors.affiliation: a Stem Cell Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Hojjatollah
authors.initials: H
authors.lastname: Nozad Charoudeh
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D019089:Stem Cell Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D015533:Transcriptional Activation; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
chemical_list: D016207:Cytokines; D020569:Proto-Oncogene Proteins c-rel; D034741:RNA, Small Interfering; D019089:Stem Cell Factor; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: CD34+ cells; FLT3; NF-κB; c-Rel; cord blood; cytokines; siRNA; stem cell factor (SCF)