Tuftsin Promotes an Anti-Inflammatory Switch and Attenuates Symptoms in Experimental Autoimmune Encephalomyelitis

Wu, Muzhou; Nissen, Jillian C.; Chen, Emily I.; Tsirka, Stella E.

doi:10.1371/journal.pone.0034933

Cited by 38 publications

(53 citation statements)

References 65 publications

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“…As mentioned above, if microglia assume a more anti-inflammatory phenotype, this could induce a more neuroprotective environment in an inflammatory CNS setting, such as in MS. For example, the tetrapeptide, tuftsin (TKPR), has been seen to attenuate EAE by acting specifically on microglia and promoting an anti-inflammatory phenotype [84,85]. We have shown that tuftsin signals, through its receptor neuropilin-1, present on microglia to induce canonical TGF-β signaling, resulting in the release of the anti-inflammatory cytokines TGF-β and IL-10, both of which have been seen to promote neuroprotection [86].…”

Section: The Neuroprotective Potential Of Microgliamentioning

confidence: 99%

The Diverse Roles of Microglia in the Neurodegenerative Aspects of Central Nervous System (CNS) Autoimmunity

Thompson

Tsirka

2017

IJMS

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Autoimmune diseases of the central nervous system (CNS) involve inflammatory components and result in neurodegenerative processes. Microglia, the resident macrophages of the CNS, are the first responders after insults to the CNS and comprise a major link between the inflammation and neurodegeneration. Here, we will focus on the roles of microglia in two autoimmune diseases: the prevalent condition of multiple sclerosis (MS) and the much rarer Rasmussen’s encephalitis (RE). Although there is an abundance of evidence that microglia actively contribute to neuronal damage in pathological states such as MS and RE, there is also evidence of important reparative functions. As current research supports a more complex and diverse array of functions and phenotypes that microglia can assume, it is an especially interesting time to examine what is known about both the damaging and restorative roles that microglia can play in the inflammatory CNS setting. We will also discuss the pharmacological approaches to modulating microglia towards a more neuroprotective state.

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Section: The Neuroprotective Potential Of Microgliamentioning

confidence: 99%

The Diverse Roles of Microglia in the Neurodegenerative Aspects of Central Nervous System (CNS) Autoimmunity

Thompson

Tsirka

2017

IJMS

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“…Recently, researchers have developed a variety of reagents, such as resveratrol, neuropeptide Y (NPY), valproic acid, tuftsin and fasudil in the treatment of EAE and MS [48,50,64,68,69]. The treated mice usually have lower levels of TNF-α, IL-1β, IL-6, IL-12/23p40 and free radical NO, but higher levels of IL-10 and arginase-1 from CD206+ M2 cells at the peak of EAE (day 14), displaying a M2 cell biased polarization after the treatment [48].…”

Section: Macrophages In Eaementioning

confidence: 99%

Macrophages: A double-edged sword in experimental autoimmune encephalomyelitis

2014

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Multiple sclerosis (MS) is a debilitating neurological disorder of the central nervous system (CNS), characterized by activation and infiltration of leukocytes and dendritic cells into the CNS. In the initial phase of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), peripheral macrophages infiltrate into the CNS, where, together with residential microglia, they participate in the induction and development of disease. During the early phase, microglia/macrophages are immediately activated to become classically activated macrophages (M1 cells), release pro-inflammatory cytokines and damage CNS tissue. During the later phase, microglia/macrophages in the inflamed CNS are less activated, present as alternatively activated macrophage phenotype (M2 cells), releasing anti-inflammatory cytokines, accompanied by inflammation resolution and tissue repair. The balance between activation and polarization of M1 cells and M2 cells in the CNS is important for disease progression. Pro-inflammatory IFN-[H9253] and IL-12 drive M1 cell polarization, while IL-4 and IL-13 drive M2 cell polarization. Given that polarized macrophages are reversible in a well-defined cytokine environment, macrophage phenotypes in the CNS can be modulated by molecular intervention. This review summarizes the detrimental and beneficial roles of microglia and macrophages in the CNS, with an emphasis on the role of M2 cells in EAE and MS patients.

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“…Inhibition of microglial activation by either the tripeptide macrophage/microglial inhibitory factor MIF (TKP) or minocycline ameliorates EAE symptoms [17]–[19]. Moreover, we have shown that shifting microglial activation towards an M2 state leads to a corresponding shift of T cells towards immunoprotective phenotypes, resulting in improved EAE outcomes [20]. Therefore, microglia have key roles in determining MS/EAE pathogenic outcomes, and pharmacological fine-tuning of their function could greatly affect disease progression.…”

Section: Introductionmentioning

confidence: 99%

The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

Gao

Nissen

et al. 2014

PLoS ONE

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Epidemiological studies have reported that cigarette smoking increases the risk of developing multiple sclerosis (MS) and accelerates its progression. However, the molecular mechanisms underlying these effects remain unsettled. We have investigated here the effects of the nicotine and the non-nicotine components in cigarette smoke on MS using the experimental autoimmune encephalomyelitis (EAE) model, and have explored their underlying mechanism of action. Our results show that nicotine ameliorates the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an EAE/MS therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC), accelerated and increased adverse clinical symptoms during the early stages of EAE, and we identify a particular cigarette smoke compound, acrolein, as one of the potential mediators. We also show that the mechanisms underlying the opposing effects of nicotine and CSC on EAE are likely due to distinct effects on microglial viability, activation, and function.

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Tuftsin Promotes an Anti-Inflammatory Switch and Attenuates Symptoms in Experimental Autoimmune Encephalomyelitis

Cited by 38 publications

References 65 publications

The Diverse Roles of Microglia in the Neurodegenerative Aspects of Central Nervous System (CNS) Autoimmunity

The Diverse Roles of Microglia in the Neurodegenerative Aspects of Central Nervous System (CNS) Autoimmunity

Macrophages: A double-edged sword in experimental autoimmune encephalomyelitis

The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

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