Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice

Wu, Bangwei; Meng, Kai; Ji, Qingwei; Cheng, Min; Yu, Kunwu; Zhao, Xiaoqi; Tony, Hasahya; Liu, Yingying; Zhou, Yujie; Chang, Chao; Zhong, Yucheng; Zhu, Zhengfeng; Zhang, W.; Mao, Xiaobo; Zeng, Qiutang

doi:10.1111/cei.12284

Cited by 103 publications

(109 citation statements)

References 51 publications

(104 reference statements)

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“…The inhibitory effects of IL-37 on innate immune response have been studied using cells transfected or silenced with IL-37, mice treated with recombinant or plasmid-DNA IL-37, and IL-37tg mice (2,3,(8)(9)(10)(11)(12). In the present study, we not only demonstrated the inhibitory effects of IL-37 on adaptive immune response, but also provided evidence that IL-37 promotes generation of semimature tolerogenic DCs.…”

Section: Discussionsupporting

confidence: 63%

“…Compared with WT mice, mice expressing human IL-37b (IL-37tg mice) produce lower amounts of proinflammatory cytokines after lipopolysaccharide (LPS) administration and are protected from LPS-induced septic shock (3) and dextran sulfate sodium-induced colitis (8). Administration of recombinant human IL-37 in mice suppresses cytokine and chemokine production, neutrophil infiltration, and cell death, thereby ameliorating hepatic and myocardial ischemia/reperfusion injury (9,10). Treatment of mice with human IL-37 plasmid-DNA reduces local and systemic inflammation in Con A-induced hepatitis and psoriasis (11,12).…”

mentioning

confidence: 99%

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Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells

Luo¹,

Cai

Liu³

et al. 2014

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

150

177

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IL-1 family member IL-37 limits innate inflammation in models of colitis and LPS-induced shock, but a role in adaptive immunity remains unknown. Here, we studied mice expressing human IL-37b isoform (IL-37tg) subjected to skin contact hypersensitivity (CHS) to dinitrofluorobenzene. CHS challenge to the hapten was significantly decreased in IL-37tg mice compared with wild-type (WT) mice (−61%; P < 0.001 at 48 h). Skin dendritic cells (DCs) were present and migrated to lymph nodes after antigen uptake in IL-37tg mice. When hapten-sensitized DCs were adoptively transferred to WT mice, antigen challenge was greatly impaired in mice receiving DCs from IL-37tg mice compared with those receiving DCs from WT mice (−60%; P < 0.01 at 48 h). In DCs isolated from IL-37tg mice, LPS-induced increase of MHC II and costimulatory molecule CD40 was reduced by 51 and 31%, respectively. In these DCs, release of IL-1β, IL-6, and IL-12 was reduced whereas IL-10 secretion increased (37%). Consistent with these findings, DCs from IL-37tg mice exhibited a lower ability to stimulate syngeneic and allogeneic naive T cells as well as antigen-specific T cells and displayed enhanced induction of T regulatory (Treg) cells (86%; P < 0.001) in vitro. Histological analysis of CHS skin in mice receiving hapten-sensitized DCs from IL-37tg mice revealed a marked reduction in CD8 + T cells (−74%) but an increase in Treg cells (2.6-fold). Together, these findings reveal that DCs expressing IL-37 are tolerogenic, thereby impairing activation of effector T-cell responses and inducing Treg cells. IL-37 thus emerges as an inhibitor of adaptive immunity.tolerance | skin inflammation | allergic contact dermatitis I nterleukin-37 (IL-37; formerly IL-1 family member 7) isoform b inhibits innate inflammation (1-3). In human peripheral blood from healthy subjects, low levels of steady-state IL-37 mRNA and protein are expressed in monocytes, dendritic cells (DCs), and plasma cells perhaps due to instability elements within the coding region (4, 5); however, stimulation with proinflammatory cytokines or Toll-like receptor (TLR) ligands induces IL-37 levels, which in turn suppress the proinflammatory cytokines IL-1α, IL-1β, IL-6, M-CSF, and GM-CSF but not anti-inflammatory cytokines IL-10 and IL-1Ra (4-7). Although an ORF for the murine homolog of IL37 is absent in various mouse databases, human IL-37 expression in a variety of human and murine cells inhibits innate immunity and suppresses production of proinflammatory cytokines and chemokines (2,3,8), indicating that human IL-37 is functional in murine cells. Compared with WT mice, mice expressing human IL-37b (IL-37tg mice) produce lower amounts of proinflammatory cytokines after lipopolysaccharide (LPS) administration and are protected from LPS-induced septic shock (3) and dextran sulfate sodium-induced colitis (8). Administration of recombinant human IL-37 in mice suppresses cytokine and chemokine production, neutrophil infiltration, and cell death, thereby ameliorating hepatic and myocardial ischemia/reperfu...

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Section: Discussionsupporting

confidence: 63%

mentioning

confidence: 99%

Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells

Luo¹,

Cai

Liu³

et al. 2014

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

150

177

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“…Notably, administration of recombinant IL-37 ameliorates myocardial ischemial injury or hepatic ischemia/reperfusion injury during acute phase in mouse models. 39,40 According to our results, it is speculated that extracellular IL-37 probably contribute to vascular repair in ischemic injury through promoting angiogenesis in addition to its anti-inflammatory function. …”

Section: Discussionmentioning

confidence: 69%

IL-37 Is a Novel Proangiogenic Factor of Developmental and Pathological Angiogenesis

Yang

Lin

Zhao

et al. 2015

ATVB

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Objective— Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Interleukin 37 (IL-37) is a newly identified cytokine of the IL-1 family, some members of which are important in inflammation and angiogenesis. However, the function of IL-37 in angiogenesis remains unknown. We aimed to explore the regulatory role of IL-37 in pathological and physiological angiogenesis. Approach and Results— We found that IL-37 was expressed and secreted in endothelial cells and upregulated under hypoxic conditions. IL-37 enhanced endothelial cell proliferation, capillary formation, migration, and vessel sprouting from aortic rings with potency comparable with that of vascular endothelial growth factor. IL-37 activates survival signals including extracellular signal-regulated kinase 1/2 and AKT in endothelial cells. IL-37 promoted vessel growth in implanted Matrigel plug in vivo in a dose-dependent manner with potency comparable with that of basic fibroblast growth factor. In the mouse model of retinal vascular development, neonatal mice administrated with IL-37 displayed increased neovascularization. We demonstrated further that IL-37 promoted pathological angiogenesis in the mouse model of oxygen-induced retinopathy. Conclusions— Our findings suggest that IL-37 is a novel and potent proangiogenic cytokine with essential role in pathophy siological settings.

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“…The abundance of IL-37 transcripts is low in PBMCs and DCs is due to an instability sequence in IL37. This instability sequence limits mRNA half-life of IL-37 [33] . Indeed, despite having a CMV promoter, resting mRNA levels for IL-37 in IL37-tg mice is either absent or low but rapidly increases with inflammation [23] .…”

Section: Il-37 and Its Receptormentioning

confidence: 99%

The anti-Inflammatory activity of Interleukin-37 in Behçet’s disease

Hamzaoui

2016

Inflamm Cell Signal

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Behçet's disease (BD), a systemic vasculitis disorder is associated with the Silk Road. Oral aphtous and genital ulcers, cutaneous pseudo folliculitis and uveitis are the most common manifestations. These manifestations are frequently associated with neurological symptoms, pulmonary involvement and arthritis. The etiology remains uncertain and the most fashionable hypothesis is immunological. BD disease is thought to be caused by pathogenic helper T (Th) cells. Th1, Th2, Th17 and Treg cells have been implicated in its pathogenesis. Recently spotlight has been drawn to novel cytokine of the IL-1 family: interleukin-37 (IL-37). Since its discovery, IL-37 has been studied extensively in immunological field. It has been established that IL-37 inhibits innate and adaptive immunity through suuppression of pro-inflammatory molecules. This review will discuss the role of IL-37 in BD.

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Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice

Cited by 103 publications

References 51 publications

Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells

Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells

IL-37 Is a Novel Proangiogenic Factor of Developmental and Pathological Angiogenesis

The anti-Inflammatory activity of Interleukin-37 in Behçet’s disease

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