Is Interleukin-38 a key player cytokine in atherosclerosis immune gene therapy?

Esmaeilzadeh, Abdolreza; Pouyan, Shabnam; Erfanmanesh, Maryam

doi:10.1016/j.mehy.2019.02.048

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…Whether Anti-IL-38 Abs have the same effect on AVMC in female mice requires further assessment. Second, it has been shown that IL-38 binds to IL-36R and exerts its effects by antagonizing the activation of intracellular signaling pathways such as JNK/AP1, p38 MAPK, ERK1/2, and NF-κB [ 14 , 35 ], which have been widely confirmed to be involved in the pathogenesis of AVMC [ 2 , 5 , 6 ]. Studies on the downstream signaling pathway of IL-38 will help reveal its regulatory mechanisms in AVMC in more detail.…”

Section: Discussionmentioning

confidence: 99%

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Xue

Chen

et al. 2021

Virol J

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Background Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. Methods Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected. Results The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication. Conclusions Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.

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Section: Discussionmentioning

confidence: 99%

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Xue

Chen

et al. 2021

Virol J

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“…For instance, risk factors such as hyperlipidemia, hypertension, and diabetes can exacerbate inflammatory responses (like suppression of anti‐inflammatory cytokines and enhancement of pro‐inflammatory cytokines) by increasing and activating macrophages, dendritic cells (DCs), and nonspecific memory cells, which in turn promotes the occurrence of atherosclerosis, eventually leading to the occurrence of IS. IL‐38 was shown to prevent atherosclerosis and reduce the incidence and risk of cardiovascular and cerebrovascular events 20,124–127 . IL‐38 can suppress inflammation and reduce pathological damage by regulating innate and adaptive immunity 128 .…”

Section: The Putative Effects and Mechanisms Of Il‐38 Underpinning Cn...mentioning

confidence: 99%

Emerging functions and therapeutic targets of IL‐38 in central nervous system diseases

Gao,

Cai,

et al. 2024

CNS Neurosci Ther

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Interleukin (IL)‐38 is a newly discovered cytokine of the IL‐1 family, which binds various receptors (i.e., IL‐36R, IL‐1 receptor accessory protein‐like 1, and IL‐1R1) in the central nervous system (CNS). The hallmark physiological function of IL‐38 is competitive binding to IL‐36R, as does the IL‐36R antagonist. Emerging research has shown that IL‐38 is abnormally expressed in the serum and brain tissue of patients with ischemic stroke (IS) and autism spectrum disorder (ASD), suggesting that IL‐38 may play an important role in neurological diseases. Important advances include that IL‐38 alleviates neuromyelitis optica disorder (NMOD) by inhibiting Th17 expression, improves IS by protecting against atherosclerosis via regulating immune cells and inflammation, and reduces IL‐1β and CXCL8 release through inhibiting human microglial activity post‐ASD. In contrast, IL‐38 mRNA is markedly increased and is mainly expressed in phagocytes in spinal cord injury (SCI). IL‐38 ablation attenuated SCI by reducing immune cell infiltration. However, the effect and underlying mechanism of IL‐38 in CNS diseases remain inadequately characterized. In this review, we summarize the biological characteristics, pathophysiological role, and potential mechanisms of IL‐38 in CNS diseases (e.g., NMOD, Alzheimer's disease, ASD, IS, TBI, and SCI), aiming to explore the therapeutic potential of IL‐38 in the prevention and treatment of CNS diseases.

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“…A. Esmaeilzadeh и соавт. продемонстрировали, что IL-38 блокировал сигнальные пути NK-κB, AP-1 и уменьшал образование атероматозного ядра [40].…”

Section: обнаружение в кровиunclassified

Interleukin-38 and cardiovascular pathology: literature review

Alieva,

Baykova,

Pinchuk

et al. 2023

CardioSomatics

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Cardiovascular pathology is a leading cause of morbidity and mortality. An important task of modern cardiology is the search and study of new biological markers. Scientists’ interest is actively focused on the study of interleukin-38. Interleukin-38 is an anti-inflammatory cytokine and a member of the interleukin-1 family. This study aimed to analyze literature sources devoted to the study of interleukin-38 as a cardiovascular biological marker. Literature sources, including all relevant publications in PubMed (MEDLINE), RSCI, Google Scholar, and Science Direct, were analyzed. The search depth was 9 years. Interleukin-38 is found in the skin, heart, placenta, fetal liver, spleen, thymus, and activated B cells of the tonsils. Interleukin-38 protein is detected in human plasma, serum, and cell cultures by enzyme-linked immunosorbent assay. Interleukin-38 regulates immune and inflammatory responses by binding to its receptors and activating downstream signals. Its deficiency is associated with increased systemic inflammation in aging, cardiovascular diseases, and metabolic diseases. Currently, not much clinical and experimental data have been accumulated regarding the effect of interleukin-38 on the cardiovascular system; however, further studies are expected to demonstrate the possibility of its use as an additional laboratory tool for diagnosis and assessment of prognosis in patients with cardiac problems. Regulating the concentration and expression of interleukin-38 is a promising strategy for the treatment of cardiovascular diseases.

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Is Interleukin-38 a key player cytokine in atherosclerosis immune gene therapy?

Cited by 9 publications

References 40 publications

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Emerging functions and therapeutic targets of IL‐38 in central nervous system diseases

Interleukin-38 and cardiovascular pathology: literature review

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