Naturally derived Heme-Oxygenase 1 inducers attenuate inflammatory responses in human dendritic cells and T cells: relevance for psoriasis treatment

Campbell, Nicole K.; Fitzgerald, Hannah K.; Malara, Anna; Hambly, Róisín; Sweeney, Cheryl; Kirby, Brian; Fletcher, Jean M.; Dunne, Aisling

doi:10.1038/s41598-018-28488-6

Cited by 45 publications

(52 citation statements)

References 65 publications

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“…The regulation of metabolism by the two polyphenols is via activation of AMPK, which results in the inhibition of mTOR signaling [ 18 ]. Carnosol and curcumin also upregulate heme oxygenase-1 (HO-1), which is an important anti-inflammatory and antioxidant enzyme [ 232 ]. Recently, an untargeted metabolomics study has revealed the induction of anti-inflammatory prostaglandin pathway and modulation of gut microbiota by the consumption of curcumin-containing curcuma longa L. extract [ 233 ].…”

Section: Effect Of Polyphenols On the Composition Of Gut Microbiotmentioning

confidence: 99%

Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism

Man¹,

Zhou²,

Xia³

et al. 2020

Nutrients

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Immunological and metabolic processes are inextricably linked and important for maintaining tissue and organismal health. Manipulation of cellular metabolism could be beneficial to immunity and prevent metabolic and degenerative diseases including obesity, diabetes, and cancer. Maintenance of a normal metabolism depends on symbiotic consortium of gut microbes. Gut microbiota contributes to certain xenobiotic metabolisms and bioactive metabolites production. Gut microbiota-derived metabolites have been shown to be involved in inflammatory activation of macrophages and contribute to metabolic diseases. Recent studies have focused on how nutrients affect immunometabolism. Polyphenols, the secondary metabolites of plants, are presented in many foods and beverages. Several studies have demonstrated the antioxidant and anti-inflammatory properties of polyphenols. Many clinical trials and epidemiological studies have also shown that long-term consumption of polyphenol-rich diet protects against chronic metabolic diseases. It is known that polyphenols can modulate the composition of core gut microbiota and interact with the immunometabolism. In the present article, we review the mechanisms of gut microbiota and its metabolites on immunometabolism, summarize recent findings on how the interaction between microbiota and polyphenol modulates host immunometabolism, and discuss future research directions.

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Section: Effect Of Polyphenols On the Composition Of Gut Microbiotmentioning

confidence: 99%

Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism

Man¹,

Zhou²,

Xia³

et al. 2020

Nutrients

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show abstract

“…Currently, the exact cellular mechanism of HO-1 induced immunosuppressive effects is still unclear. However, studies suggest that a large component may be attributed to the ability of HO-1 and the HO-1 catalyzed end products bilirubin and CO in inhibiting dendritic cell (DC) function (31)(32)(33). A recent study demonstrated that induction of HO-1 hinders DC maturation in vitro (31).…”

Section: Heme Oxygenase-1 In Immune Regulationmentioning

confidence: 99%

“…However, studies suggest that a large component may be attributed to the ability of HO-1 and the HO-1 catalyzed end products bilirubin and CO in inhibiting dendritic cell (DC) function (31)(32)(33). A recent study demonstrated that induction of HO-1 hinders DC maturation in vitro (31). This resulted in limited antigen presentation and activation of adaptive T cell responses as DCs after HO-1 induction exhibited diminished ability to stimulate proliferation of allogeneic CD4+ T cells (31).…”

Section: Heme Oxygenase-1 In Immune Regulationmentioning

confidence: 99%

“…A recent study demonstrated that induction of HO-1 hinders DC maturation in vitro (31). This resulted in limited antigen presentation and activation of adaptive T cell responses as DCs after HO-1 induction exhibited diminished ability to stimulate proliferation of allogeneic CD4+ T cells (31). Other studies show that induction of HO-1 inhibited production of the pro-inflammatory cytokines IL-12, IL-6, TNFa and type 1 interferons without inhibiting production of the anti-inflammatory cytokine IL-10 (32,33).…”

Section: Heme Oxygenase-1 In Immune Regulationmentioning

confidence: 99%

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Tolerance to FVIII: Role of the Immune Metabolic Enzymes Indoleamine 2,3 Dyoxigenase-1 and Heme Oxygenase-1

et al. 2020

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The occurrence of neutralizing anti-FVIII antibodies is a major complication in the treatment of patients affected by hemophilia A. The immune response to FVIII is a complex, multi-factorial process that has been extensively studied for the past two decades. The reasons why only a proportion of hemophilic patients treated with FVIII concentrates develop a clinically significant immune response is incompletely understood. The "danger theory" has been proposed as a possible explanation to interpret the findings of some observational clinical studies highlighting the possible detrimental impact of inflammatory stimuli at the time of replacement therapy on inhibitor development. The host immune system is often challenged to react to FVIII under steady state or inflammatory conditions (e.g., bleeding, infections) although fine tuning of mechanisms of immune tolerance can control this reactivity and promote longterm unresponsiveness to the therapeutically administered factor. Recent studies have provided evidence that multiple interactions involving central and peripheral mechanisms of tolerance are integrated by the host immune system with the environmental conditions at the time of FVIII exposure and influence the balance between immunity and tolerance to FVIII. Here we review evidences showing the involvement of two key immunoregulatory oxygenase enzymes (IDO1, HO-1) that have been studied in hemophilia patients and pre-clinical models, showing that the ability of the host immune system to induce such regulatory proteins under inflammatory conditions can play important roles in the balance between immunity and tolerance to exogenous FVIII.

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“…Meta-analysis shows that curcumin supplementation significantly reduces concentration of circulating IL-6, a key regulator of the immune system, with more evident effect in patients with higher degree of systemic inflammation [ 51 ], indicating that curcumin can effectively inhibit inflammation propagation. In human dendritic cells (DCs), curcumin treatment limits DC maturation, reduces proinflammatory cytokine production, and prevents induction of allospecific T cell responses [ 52 ]. In the mononuclear cells from AD patients, curcuminoid compound reverses defective phagocytosis of A β and expression depression of TLRs such as TLRs 2–4, reflecting its ability to correct immune defects [ 53 , 54 ].…”

Section: Systemic Immunity Regulation By Phytochemicals and Its Comentioning

confidence: 99%

Connection between Systemic Inflammation and Neuroinflammation Underlies Neuroprotective Mechanism of Several Phytochemicals in Neurodegenerative Diseases

Wang

Song

Zheng

et al. 2018

Oxidative Medicine and Cellular Longevity

112

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Oxidative damage, mitochondrial dysfunction, and neuroinflammation are strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), and a substantial portion of elderly population at risk of these diseases requires nutritional intervention to benefit health due to lack of clinically relevant drugs. To this end, anti-inflammatory mechanisms of several phytochemicals such as curcumin, resveratrol, propolis, polyunsaturated fatty acids (PUFAs), and ginsenosides have been extensively studied. However, correlation of the phytochemicals with neuroinflammation or brain nutrition is not fully considered, especially in their therapeutic mechanism for neuronal damage or dysfunction. In this article, we review the advance in antioxidative and anti-inflammatory effects of phytochemicals and discuss the potential communication with brain microenvironment by improved gastrointestinal function, enhanced systemic immunity, and neuroprotective outcomes. These data show that phytochemicals may modulate and suppress neuroinflammation of the brain by several approaches: (1) reducing systemic inflammation and infiltration via the blood-brain barrier (BBB), (2) direct permeation into the brain parenchyma leading to neuroprotection, (3) enhancing integrity of disrupted BBB, and (4) vagal reflex-mediated nutrition and protection by gastrointestinal function signaling to the brain. Therefore, many phytochemicals have multiple potential neuroprotective approaches contributing to therapeutic benefit for pathogenesis of neurodegenerative diseases, and development of strategies for preventing these diseases represents a considerable public health concern and socioeconomic burden.

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Naturally derived Heme-Oxygenase 1 inducers attenuate inflammatory responses in human dendritic cells and T cells: relevance for psoriasis treatment

Cited by 45 publications

References 65 publications

Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism

Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism

Tolerance to FVIII: Role of the Immune Metabolic Enzymes Indoleamine 2,3 Dyoxigenase-1 and Heme Oxygenase-1

Connection between Systemic Inflammation and Neuroinflammation Underlies Neuroprotective Mechanism of Several Phytochemicals in Neurodegenerative Diseases

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