15 research outputs found
Gene expression of inhibitory receptors and immune regulatory molecules in polarized macrophages derived from early- and late-stage BD patients
Background: Bipolar disorder (BD) has been associated with increased levels of peripheral inflammatory mediators and neuroinflammation. Previously, we observed different immune responses in macrophages of BD patients at different stages of the disorder. Thus, we aimed to further evaluate the regulation of immune response in BD by quantifying the expression of immune checkpoint receptors and respective ligands, as well as molecules involved in regulation and transcription of inflammatory mediators in polarized macrophages of early and late stages individuals with BD. Methods: qRT-PCR was performed to analyze the expression of genes involved in immune regulation, such as TLR1, TLR6, PD-1, NFKB1, PD-L1, PD-L2 and TIM-3 in samples of proinflammatory M1 or M(IFNγ+LPS) and anti-inflammatory M2 or M(IL-4) macrophages derived from peripheral blood mononuclear cells (PBMCs) of euthymic BD patients (n=16), classified as early-stage BD (BD-E, n=9) and late-stage BD (BD-L, n=7) - according to Functional Assessment Short Test (FAST) - and healthy controls (HC, n=10). Results: M(IL-4) from BD-E showed higher expression levels of NFKB1 and PD-L1 in comparison to HC (p<0.05), while BD-L only had higher expression levels of PD-L1 compared to HC (p<0.05). No statistical differences were found between groups for the expression levels of TLR1, PD-L2 and TIM-3 in M(IL-4) phenotype, while expression levels remained unchanged in M(IFNγ+LPS) for all markers. TLR6 and PD-1 did not show PCR amplification in both macrophages phenotypes. Conclusion: Our findings suggest an immunological regulation acting as a compensatory mechanism by M2 anti-inflammatory macrophages at early stage of BD, although decreased regulation in these cells seems to be observed at late stages of the disorder. On the other hand, the impairment function of proinflammatory macrophages at late stages of BD might underlie a different immunologic mechanism, such as senescence. We hypothesize that such alterations are possibly due to persistent chronic low-grade inflammation during the course of BD that results in the ‘exhaustion’ of macrophage response. However, further investigation is required to better comprehend the role of immune regulatory mechanisms in the disorder
Correlação de comportamento tipo-anedônico com IFNγ sérico em um modelo de depressão two-hit em ratos
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report
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