Altered intracellular signaling cascades in peripheral blood mononuclear cells from BD patients.
Bipolar disorder (BD) is a severe psychiatric disorder of complex physiopathology that has been associated with a pro-inflammatory state. The aim of the present study was to investigate intracellular pathways associated with inflammatory signaling, assessing the phosphorylation levels of transcription factor nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) in peripheral blood mononuclear cells of euthymic BD patients and healthy controls. Fifteen BD euthymic type I patients, and 12 healthy controls matched by age and gender were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients also by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Phosphorylation levels of p65 NF-κB subunit, and MAPK ERK1/2, and p38 were assessed by Western blot and flow cytometry. Plasma cytokines (IL-2, IL-4, IL6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured using cytometric bead arrays. Western blot and flow cytometry analyses showed increased phosphorylation levels of p65 NF-κB subunit, and MAPKs ERK1/2, and p38 in BD patients in euthymia in comparison with controls. BD patients presented increased pro-inflammatory cytokines levels in comparison with controls, and TNF-α correlated with the levels of phosphorylated p65 NF-κB. The present study found increased activation of MAPK and NF-κB pathways in BD patients, which is in line with a pro-inflammatory status.
Programa de Pós Graduação em Neurociências, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Laboratório Interdisciplinar de Investigação Médica (LIIM), Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: izabelagb@gmail.com.
Izabela Guimarães
IG
Barbosa
Camila R C
CR
Nogueira
Natália Pessoa
NP
Rocha
Ana Luiza Lemos
AL
Queiroz
Juliana Priscila
JP
Vago
Luciana Pádua
LP
Tavares
Frankcinéia
F
Assis
Caio Tavares
CT
Fagundes
Rodrigo Barreto
RB
Huguet
Moisés Evandro
ME
Bauer
Antônio Lúcio
AL
Teixeira
Lirlândia Pires
LP
de Sousa
D000328:Adult; D001714:Bipolar Disorder / Q000097:blood*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011569:Psychiatric Status Rating Scales; D019892:eIF-2 Kinase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D019892:eIF-2 Kinase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
Bipolar disorder; Immunology; Inflammation; MAPK; Mania; Nuclear factor kappa B