The effects of IL-18BP on mRNA expression of inflammatory cytokines and apoptotic genes in renal injury induced by infrarenal aortic occlusion

Gönül, Yücel; Genç, Abdurrahman; Ahsen, Ahmet; Bal, Ahmet; Hazman, Ömer; Toktaş, Muhsin; Ulu, Memnune Sena; Özdinç, Şerife; Songür, Ahmet

doi:10.1016/j.jss.2015.12.026

Cited by 13 publications

(7 citation statements)

References 49 publications

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“…As a common autoimmune disease, AS has a complicated pathogenesis mechanism, which is closely related to the body's immune functions (Gönül et al, 2016). Helper T cells (Th) can be sub-divided into different sub-populations, which play important roles in the pathogenesis and progression of several autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis

et al. 2017

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“…Recombinant human IL-18BPa (rhIL-18BP, Cat No. 119-BP; R&D Systems, Minneapolis) was used in this study because human and murine IL-18BP isoforms are active across species 30 and has been used in rat and mouse studies 20 , 21 , 31 , 32 . rhIL-18BP is a water soluble small molecule and was freshly prepared with saline.…”

Section: Methodsmentioning

confidence: 99%

“…The effects of IL-18 have been implicated in many diseases including autoimmune diseases 15 , cardiovascular diseases 16 – 18 , neurovascular EC damage 19 , infrarenal aortic occlusion-mediated renal injury 20 , hemophagocytic lyphohistiocytosis 21 , and inflammatory bowel disease 22 in clinical and animal studies. IL-18BP and anti-IL-18 antibody have been used to neutralize IL-18 and treat these diseases.…”

Section: Introductionmentioning

confidence: 99%

IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

Cui

Hull

et al. 2020

Sci Rep

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Recent studies suggested that radiation exposure causes local and systemic inflammatory responses and induces cell and tissue damage. We have reported that IL-18 plays an important role in radiation-induced injury. Here, we demonstrate that IL-18 binding protein (IL-18BP), a natural antagonist of IL-18, was significantly increased (1.7–63 fold) in mouse serum on day 1 after 0.5–10 Gy TBI. However, this high level of IL-18BP was not sufficient to neutralize the active IL-18 in irradiated mice, resulting in a radiation dose-dependent free IL-18 increase in these mice’s serum which led to pathological alterations to the irradiated cells and tissues and finally caused animal death. Administration of recombinant human (rh) IL-18BP (1.5 mg/kg) with single (24, 48 or 72 h post-TBI) or double doses (48 h and 5 days post-TBI) subcutaneous (SC) injection increased 30-day survival of CD2F1 mice after 9 Gy TBI 12.5–25% compared with the vehicle control treated group, respectively. Furthermore, the mitigative effects of rhIL-18BP included balancing the ratio of IL-18/IL-18BP and decreasing the free IL-18 levels in irradiated mouse serum and significantly increasing blood cell counts, BM hematopoietic cellularity and stem and progenitor cell clonogenicity in mouse BM. Furthermore, IL-18BP treatment inhibited the IL-18 downstream target interferon (IFN)-γ expression in mouse BM, decreased reactive oxygen species (ROS) level in the irradiated mouse heart tissues, attenuated the stress responsive factor GDF-15 (growth differentiation factor-15) and increased the intestine protector citrulline level in total body irradiated mouse serum, implicating that IL-18BP may protect multiple organs from radiation-induced inflammation and oxidative stress. Our data suggest that IL-18 plays a key role in radiation-induced cell and tissue damage and dysfunction; and for the first time demonstrated that IL-18BP counters IL-18 activation and therefore may mitigate/treat radiation-induced multiple organ injuries and increase animal survival with a wider therapeutic window from 24 h and beyond after lethal doses of radiation exposure.

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“…NF-κB, a ubiquitous family of transcription factors, is involved in a variety of essential processes in the body including inflammation, immunity, and cell proliferation and survival (31). AS is a common autoimmune disease, and its pathogenesis is closely related to immune function (32).…”

Section: Alleviated Activation Of the Nlrp3 Inflammasome And Maintain...mentioning

confidence: 99%

Micheliolide alleviates ankylosing spondylitis (AS) by suppressing the activation of the NLRP3 inflammasome and maintaining the balance of Th1/Th2 via regulating the NF-κB signaling pathway

Tian¹,

Yao²,

Chen³

2020

Ann Transl Med

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Background: Ankylosing spondylitis (AS) is a common form of inflammatory arthritis. Micheliolide (MCL), a sesquiterpene lactone, is reportedly involved in the alleviation of inflammatory response. This study aimed to investigate the mechanism of MCL in the treatment of AS.Methods: Mice were randomly divided into five groups: the sham group, the MCL (50 mg/kg) group, the AS model group, the AS + MCL (20 mg/kg) group, and the AS + MCL (50 mg/kg) group. After the addition of the inhibitor celastrol, mice were randomly divided into five groups: the sham group, the AS model group, the AS + MCL (50 mg/kg) group, the AS + Celastrol (1 mg/kg) group, and the AS + Celastrol (1 mg/kg) + MCL (50 mg/kg) group. Results:Compared with the AS model mice, the protein expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18 were decreased after MCL treatment. The protein expression levels of capase-1 p10, IL-1β p17, NOD-like receptor family and pyrin domain containing 3 (NLRP3), caspase-1, and apoptosis-associated speck-like protein (ASC) were also reduced. The protein expression levels of Interferon (IFN)-γ were down-regulated, but levels of IL-4 were increased. Western blotting and immunohistochemistry revealed that the levels of p-IκB α were up-regulated, while the levels of phosphorylated-p65 were down-regulated. After the addition of celastrol, MCL treatment significantly reduced the levels of p-p65, NLRP3, caspase-1, and ASC. Meanwhile, the levels of IFN-γ were markedly down-regulated, but the levels of IL-4 were enhanced.Conclusions: Our study found that MCL suppressed the activation of NLRP3 inflammasome and maintained the balance of Th1/Th2 via regulating NF-κB signaling. Therefore, MCL could potentially be used to treat AS.

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The effects of IL-18BP on mRNA expression of inflammatory cytokines and apoptotic genes in renal injury induced by infrarenal aortic occlusion

Cited by 13 publications

References 49 publications

Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis

Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis

IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

Micheliolide alleviates ankylosing spondylitis (AS) by suppressing the activation of the NLRP3 inflammasome and maintaining the balance of Th1/Th2 via regulating the NF-κB signaling pathway

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