Adoptive transfer of immunomodulatory M2 macrophages suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice via blockading NF-κB pathway

Abstract

Macrophages play important roles in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), and M2 macrophage may have anti-inflammatory effects. In this study, we elucidated the roles of M1 and M2 macrophages in the pathogenesis of EAE and the effects of treatment with M2 macrophages that target certain proinflammatory cytokines and with immunomodulatory preparations that beneficially influence the disease course. We found macrophages increased at the onset of clinical signs in the EAE group, consistent with an increased proportion of M1 macrophages and low numbers of M2 macrophages. As the disease progressed and the symptoms worsened, M1 macrophages decreased and M2 macrophages gradually increased until the peak. In the recovery stage, M2 macrophages gradually decreased. Treatment with M2 macrophages inhibited the nuclear factor kappa B (NF-κB) pathway, alleviated the symptoms of EAE, reduced inflammatory cell infiltration and demyelination in the central nervous system and decreased the numbers of macrophages in the spleens. BAY-11-7082, an NF-κB blocking agent, could reduce the total number of macrophages both in vivo and in vitro, effectively prevented EAE development and significantly inhibited EAE symptoms in mice. Our study demonstrates that macrophages may play a crucial role in the pathogenesis of EAE, while M2 macrophages have anti-inflammatory effects. Transfer of M2 macrophages to EAE mice can block the NF-κB pathway successfully and relieve EAE symptoms. Application of NF-κB blockers is useful in the prevention and treatment of EAE.

Nuclear factor kappa B inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type

“…BAY11‐7082 could also diminish EAN symptoms and delay the onset of EAN by reducing M1 macrophage and proinflammatory cytokine accumulation and increasing M2 macrophage proportion in preventive group. In vitro , BAY11‐7082 inhibited the activity and proliferation of M1 macrophages, which was similar to other results [16]. Overall, these results demonstrated that the NF‐κB signaling pathway may be involved in the pathogenesis of EAN by regulating the polarization of macrophages and inhibiting the expression of inflammatory cytokines.…”

Cell therapy procedure using anti‐inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta‐analysis study

“…Interestingly, this study showed that following immediate administration of MP2 after the occurrence of a motor defect, the Peak phase of disease can be alleviated. Also, in this study, various frequencies of MP2 were transferred prior to the Peak of disease, and eventually, after the third cell injection, the Peak level was alleviated, and the Recovery phase was initiated [11]. Besides, Joanna Mikita et al treated the first dose of MP2 on the third day after EAE Onset.…”

“…The study of Xing-Mei Zhang contained the high-quality score [12], and medium quality was detected in 3 remaining papers of Chu et al, Mikita et al, and Tierney et al [11,13,14] (Table 2 and Figure 2).…”

Development of (4-Phenylamino)quinazoline Alkylthiourea Derivatives as Novel NF-κB Inhibitors

“…Moreover, while mAbs do not affect the cytokine-producing cells, several of our inhibitors, particularly 6 and 19 , selectively induced cell death in the LPS-activated macrophages, significantly stronger than the reference compound, CAPE. This could be an interesting additional effect of the novel compounds, worthy of being explored in future studies as macrophage infiltrates are especially associated with tissue damage and inflammation in metabolic syndrome [ 57 ], inflammatory brain disorders, and autoimmune diseases [ 57 , 58 ]. In addition, macrophages are implicated in the destabilization of atherosclerotic plaques, leading to acute coronary syndromes and sudden death.…”