Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-γ-independent mechanism

Fujigaki, Suwako; Saito, Kuniaki; Sekikawa, Kenji; Toné, Shigenobu; Takikawa, Osamu; Fujii, Hidehiko; Wada, Hisayasu; Noma, Akio; Seishima, Mitsuru

doi:10.1002/1521-4141(200108)31:8<2313::aid-immu2313>3.0.co;2-s

Cited by 202 publications

(151 citation statements)

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“…In our studies and those of others (15), type I IFNs are not required for IDO induction in human pDCs. IDO can be induced independent of STAT1 and IFN regulatory factor 1 by inflammatory cytokines (e.g., TNF-α, IL-6) that activate p38 MAPK and NF-κB pathways (40,41), by prostaglandin E2 acting through prostaglandin receptor EP2 (42) or by TGF-β (37,38), underscoring the complexity of signaling required for IDO induction in different cell types and physiological situations. So-called "reverse signaling" through cell surface receptors [e.g., GITR (28)] activates the noncanonical NF-κB pathway, which in synergy with IFN-α induces IDO in murine pDCs, presumably through STAT1 phosphorylation (18).…”

Section: Resultsmentioning

confidence: 99%

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Manches

Fernandez

Plumas

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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HIV modulates plasmacytoid dendritic cell (pDC) activation via Tolllike receptor 7, inducing type I IFN and inflammatory cytokines. Simultaneously, pDCs up-regulate the expression of indoleamine 2,3 dioxygenase (IDO), which is essential for the induction of regulatory T cells (Tregs), which function to down-modulate immune activation. Here we demonstrate the crucial importance of the noncanonical NF-κB pathway in the establishment of this immunoregulatory phenotype in pDCs. In response to HIV, the noncanonical NF-κB pathway directly induces IDO and involves the recruitment of TNF receptorassociated factor-3 to the Toll-like receptor/MyD88 complex, NF-κB-inducing kinase-dependent IκB kinase-α activation, and p52/RelB nuclear translocation. We also show that pDC-induced Tregs can inhibit conventional DC (cDC) maturation partially through cytotoxic T-lymphocyte antigen (CTLA)-4 engagement. Furthermore, CTLA-4 induces IDO in cDCs in a NF-κB-inducing kinase-dependent way. These CTLA-4-conditioned cDCs can in turn induce Treg differentiation in an IDO-dependent manner. Thus, the noncanonical NF-κB pathway is integral in controlling immunoregulatory phenotypes of both pDCs and cDCs.

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Section: Resultsmentioning

confidence: 99%

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Manches

Fernandez

Plumas

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…94 Cytokines may also induce depressive symptoms by affecting the serotonergic system. In fact, some cytokines, such as IFN-g, IFN-a, TNF-a and IL-1, have all been shown to upregulate the enzyme indoleamine 2,3-dioxygenase (IDO) expression [95][96][97][98] and, thus, cause increased metabolism of tryptophan, resulting in decreased availability of tryptophan to synthesize 5-HT. It has also been shown that patients treated with cytokines had decreased blood levels of tryptophan 99 and therefore it is very likely that cytokines can suppress serotonin by activating IDO that catabolizes tryptophan.…”

Section: Resultsmentioning

confidence: 99%

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

et al. 2006

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Although poststroke depression is unlikely to represent a single disorder and numerous etiologies for different kinds of poststroke depression will likely emerge as the result of future research, we believe that a number of poststroke depressive disorders are likely to be the result of specific changes in brain pathology and neurophysiology. Nevertheless, there are relatively few hypotheses about the pathophysiology of poststroke depression. This paper, therefore, proposes a new hypothesis for poststroke depression involving increased production of proinflammatory cytokines resulting from brain ischemia in cerebral areas linked to the pathogenesis of mood disorders. This paper reviews the evidence supporting the hypothesis that proinflammatory cytokines are involved in the occurrence of stroke as well as mood disorders linked to the brain damage. The increased production of proinflammatory cytokines such as IL-1b, TNF-a or IL-18 resulting from stroke may lead to an amplification of the inflammatory process, particularly in limbic areas, and widespread activation of indoleamine 2,3-dioxygenase (IDO) and subsequently to depletion of serotonin in paralimbic regions such as the ventral lateral frontal cortex, polar temporal cortex and basal ganglia. The resultant physiological dysfunction may lead to poststroke depression. Future investigations may explore this hypothesis through more extensive studies on the role of proinflammatory cytokines, such as IL-1b, TNF-a or even IL-18, in patients with poststroke depression. Molecular Psychiatry (2006) 11, 984-991.

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“…Depression could be due to a stress-related increase in the production of cytokines such as ILs, TNF-α, IFN-α, IFN-β, and IFN-γ, which, in turn, up-regulate indoleamine 2,3-dioxygenase (IDO) expression [62][63][64][65] . IDO converts tryptophan, the precursor of 5-HT, to kynurenine; so IDO activation leads to reduced levels of tryptophan and thus reduced central 5-HT synthesis [66][67][68] .…”

Section: -Hydroxytryptamine Pro-inflammatory Cytokines Havementioning

confidence: 99%

Inflammation: a mechanism of depression?

Han

2014

Neurosci. Bull.

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In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of infl ammation to depression. We fi rst briefl y introduce the infl ammatory biomarkers of depression, then discuss the sources of cytokines in the brain, and fi nally describe the neuroimmunological mechanisms underlying the association between infl ammation and depression.Keywords: depression; infl ammation; cytokines; hypothalamic-pituitary-adrenal axis; 5-HT; neuroplasticity ·Review· IntroductionThe prevalence of major depression has increased dramatically over the past few decades [1] , and women are nearly twice as likely as men to develop depressive disorder [2] . Depression is classified as a brain disorder, but its symptomatology includes some behaviors that also occur during chronic infl ammatory stress [3] . Research has shown that immune activation and the production of cytokines may be involved in depression [4] , so this relationship has received much attention. In fact, three causal pathways have been proposed: depression to inflammation, inflammation to depression, and a bidirectional relationship [5] . In this review, we focus on the impact of inflammation on depression and the underlying mechanisms. Cytokines are small cell-signaling proteins that mediate and regulate immune responses and inflammation, and can be divided into two categories:the pro-inflammatory cytokines interleukin (IL)-1 β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokines IL-1Rα, IL-4, IL-10, and transforming growth factor (TGF)-β1. Generally, t he proinfl ammatory cytokines promote systemic infl ammation and are essential for the initiation of an infl ammatory response to disease [6] , while the anti-inflammatory cytokines antagonize these actions to reduce inflammation and promote healing [6,7] . Moreover, some cytokines play dual roles [8] . In the central nervous system (CNS), the cellular source, function, and mechanisms of action of cytokines differ from those in the periphery. In the following, we briefl y introduce the current research on infl ammatory biomarkers of depression. Infl ammatory Biomarkers of DepressionSo far, there are neither universally accepted or defi nitive biomarkers of depression [9] , nor effective methods to assess the severity, endophenotypes, or response to treatment [10] .However, sufficient evidence has suggested changes in the circulating levels of cytokines in depressed patients, which can be reversed by antidepressant treatments [11,12] .So, many studies have aimed to clarify the neurobiological changes in depression and to establish inflammatory biomarkers. The peripheral levels of IL-6, TNF-α, and IL-1β are increased in patients with depression [13][14][15][16][17] , and antidepressant treatments reverse this effect [18][19][20] . These consistent results demonstrate that IL-6, TNF-α, and IL-1β are putative biomarkers for depression. However, due to the he...

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Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-γ-independent mechanism

Cited by 202 publications

References 29 publications

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

Activation of the noncanonical NF-κB pathway by HIV controls a dendritic cell immunoregulatory phenotype

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

Inflammation: a mechanism of depression?

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