title: Altered AKT1 and MAPK1 gene expression on peripheral blood mononuclear cells and correlation with T-helper-transcription factors in systemic lupus erythematosus patients.
abstract: Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE). v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1) and mitogen-activated-protein-kinase 1 (MAPK1) gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th) transcription factors (TF) gene expression, cytokines, and S100A8/S100A9-(Calprotectin). Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR)-C), T-regulatory-(Treg)-(Transforming Growth Factor Beta (TGFB)-2), and Th2-(interleukin (IL)-5)-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet)), Th2-(GATA binding protein-(GATA)-3), and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF)-α and Th0-(IL-2), Th1-(IL-12A, T-bet), GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP)-3), and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1β, IL-12(p70), Interferon-(IFN)-γ, and IL-6 cytokines were augmented. Plasma IL-1β, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity.
authors.affiliation: Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina López-Neyra-IPBLN-CSIC, Parque Tecnológico Ciencias de la Salud, Avenida Conocimiento s/n, Armilla, 18100 Granada, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Garcia-Rodriguez
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Callejas-Rubio
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Esther
authors.initials: E
authors.lastname: Zumaquero
authors.forename: Raquel
authors.initials: R
authors.lastname: Ríos-Fernandez
authors.forename: Salvador
authors.initials: S
authors.lastname: Arias-Santiago
authors.forename: Pilar
authors.initials: P
authors.lastname: Navarro
authors.forename: Jaime
authors.initials: J
authors.lastname: Sancho
authors.forename: Mercedes
authors.initials: M
authors.lastname: Zubiaur
mesh_terms: D000328:Adult; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D007375:Interleukin-1; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1