Attenuated inflammatory response of monocyte-derived macrophage from patients with BD: a preliminary report.

Autor: Ascoli BM; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil.; Postgraduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2400, Porto Alegre, RS, Brazil., Parisi MM; Laboratory of Molecular Biology and Bioinformatics, Department of Biochemistry, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, Brazil.; Postgraduate Program in Biological Sciences: Biochemistry, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, Brazil., Bristot G; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil.; Postgraduate Program in Biological Sciences: Biochemistry, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, Brazil., Antqueviezc B; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil., Géa LP; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil.; Postgraduate Program in Biological Sciences: Pharmacology and Therapeutics, UFRGS, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil., Colombo R; Laboratory of Pharmacology and Physiology, Universidade de Caxias do Sul (UCS), Rua Francisco Getúlio Vargas, 1130, Caxias Do Sul, RS, Brazil., Kapczinski F; Postgraduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2400, Porto Alegre, RS, Brazil.; Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1280 Main Street West, Hamilton, ON, Canada.; St. Joseph's Healthcare Hamilton, 100 West 5th Street, Hamilton, ON, Canada., Guma FTCR; Postgraduate Program in Biological Sciences: Biochemistry, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, Brazil.; Laboratory of Biochemistry and Cellular Biology of Lipids, Department of Biochemistry, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, Brazil., Brietzke E; Mood Disorders Molecular and Behavioral Neurosciences Research Group, Department of Psychiatry, Universidade Federal de São Paulo (USP), Rua Sena Madureira, 1500, São Paulo, SP, Brazil., Barbé-Tuana FM; Laboratory of Molecular Biology and Bioinformatics, Department of Biochemistry, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, Brazil.; Postgraduate Program in Cellular and Molecular Biology, School of Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Avenida Ipiranga, 6681, Porto Alegre, RS, Brazil., Rosa AR; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, Brazil. adrianerrosa@gmail.com.; Postgraduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2400, Porto Alegre, RS, Brazil. adrianerrosa@gmail.com.; Postgraduate Program in Biological Sciences: Pharmacology and Therapeutics, UFRGS, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil. adrianerrosa@gmail.com.
Jazyk: angličtina
Zdroj: International journal of bipolar disorders [Int J Bipolar Disord] 2019 Jun 01; Vol. 7 (1), pp. 13. Date of Electronic Publication: 2019 Jun 01.
DOI: 10.1186/s40345-019-0148-x
Abstrakt: Background: Innate immune system dysfunction has been recognized as an important element in the pathophysiology of bipolar disorder (BD). We aimed to investigate whether there are differences in the response of macrophages derived from patients in the early stages and late stages of BD and healthy subjects.
Methods: Human monocytes purified from peripheral blood mononuclear cells (PBMCs) of patients with BD type I (n = 18)-further classified into early- and late stage BD patients according to their functioning- and from healthy individuals (n = 10) were differentiated into macrophages in vitro. Monocyte-derived macrophages (M) were exposed to IFNγ plus LPS-M(IFNγ + LPS)- or IL-4-M(IL-4)-to induce their polarization into the classical (also called M1) or alternative (also called M2) activation phenotypes, respectively; or either Mψ were not exposed to any stimuli characterizing the resting state (denominated M0). In vitro secretion of cytokines, such as IL-1β, IL-6, IL-10, and TNF-α, was used as an index of macrophage activity.
Results: M(IFNγ + LPS) from late-stage BD patients produced less amount of IL-1β, IL-6, and IL-10 when compared to early-stage BD patients and healthy controls. Following alternative activation, M(IL-4) derived from late-stage patients secreted less IL-6 compared to the other groups. TNFα was less secreted by all macrophage phenotypes derived from late-stage patients when compared to healthy controls only (p < 0.005). Mψ from late-stage patients exhibited lower production of IL-1β and IL-10 compared to macrophages from healthy subjects and early-stage patients respectively. Interestingly, cytokines secretion from M(IFNγ + LPS), M(IL-4) and Mψ were similar between early-stage patients and healthy controls.
Conclusion: Our results suggest a progressive dysfunction in the response of peripheral innate immune cells of BD patients in the late stages of the illness. This failure in the regulation of the immune system function may be implicated in the multisystemic progression of BD.
Databáze: MEDLINE
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