Interleukin-8 favors pro-inflammatory activity of human monocytes/macrophages

Meniailo, Maksim Evgenievich; Малащенко, В. В.; Shmarov, V.A.; Газатова, Н. Д.; Melashchenko, Olga Borisovna; Goncharov, A. G.; Селедцова, Г. В.; Селедцов, В. И.

doi:10.1016/j.intimp.2018.01.036

Cited by 53 publications

(31 citation statements)

References 22 publications

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“…Elevated levels of these cytokines have previously been described in DM2 and CVD patients [59][60][61]. These pro-inflammatory mediators are highly pro-atherogenic as they promote differentiation to a M1-like macrophage phenotype, enhanced vascular wall recruitment and increased endothelial transmigration [62][63][64][65][66]. Thus, their overproduction likely contributes to the pathogenesis of atherosclerosis in DM2 + CVD patients on standard of care therapy.…”

Section: Discussionmentioning

confidence: 95%

BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper-activation of monocytes from patients with cardiovascular disease and type 2 diabetes

et al. 2020

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Background Patients with cardiovascular disease (CVD) and type 2 diabetes (DM2) have a high residual risk for experiencing a major adverse cardiac event. Dysregulation of epigenetic mechanisms of gene transcription in innate immune cells contributes to CVD development but is currently not targeted by therapies. Apabetalone (RVX-208) is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins—histone acetylation readers that drive pro-inflammatory and pro-atherosclerotic gene transcription. Here, we assess the impact of apabetalone on ex vivo inflammatory responses of monocytes from DM2 + CVD patients. Results Monocytes isolated from DM2 + CVD patients and matched controls were treated ex vivo with apabetalone, interferon γ (IFNγ), IFNγ + apabetalone or vehicle and phenotyped for gene expression and protein secretion. Unstimulated DM2 + CVD monocytes had higher baseline IL-1α, IL-1β and IL-8 cytokine gene expression and Toll-like receptor (TLR) 2 surface abundance than control monocytes, indicating pro-inflammatory activation. Further, DM2 + CVD monocytes were hyper-responsive to stimulation with IFNγ, upregulating genes within cytokine and NF-κB pathways > 30% more than control monocytes (p < 0.05). Ex vivo apabetalone treatment countered cytokine secretion by DM2 + CVD monocytes at baseline (GROα and IL-8) and during IFNγ stimulation (IL-1β and TNFα). Apabetalone abolished pro-inflammatory hyper-activation by reducing TLR and cytokine gene signatures more robustly in DM2 + CVD versus control monocytes. Conclusions Monocytes isolated from DM2 + CVD patients receiving standard of care therapies are in a hyper-inflammatory state and hyperactive upon IFNγ stimulation. Apabetalone treatment diminishes this pro-inflammatory phenotype, providing mechanistic insight into how BET protein inhibition may reduce CVD risk in DM2 patients.

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Section: Discussionmentioning

confidence: 95%

BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper-activation of monocytes from patients with cardiovascular disease and type 2 diabetes

et al. 2020

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“…Interestingly, damaged epithelial cells and endothelial cells per se secrete a series of chemotactic cytokines that can recruit macrophages to the site of diseased tissue (Wynn & Ramalingam, ). IL‐8 is well believed to be a key chemotactic cytokine, which is involved in the recruitment of monocyte (Meniailo et al, ). Profibrotic mediators such as TGF‐β induced proximal tubular cells to secrete IL‐8, and its production was markedly enhanced in urine proteins obtained from patients with tubular injury (Huang, Wen, Zhou, & Yu, ; Qi et al, ; Singhto & Thongboonkerd, ).…”

Section: Discussionmentioning

confidence: 99%

Follicle‐stimulating hormone promotes renal tubulointerstitial fibrosis in aging women via the AKT/GSK‐3β/β‐catenin pathway

et al. 2019

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Estrogen withdrawal in aging women contributes to the progression of chronic kidney disease (CKD). However, the effect of high circulating follicle‐stimulating hormone (FSH) levels on renal dysfunction remains unknown. In this study, blood samples from 3,055 postmenopausal women were collected and tested, which showed that there was a strong negative correlation between eGFR and FSH levels (p < 0.001), independent of LH, testosterone, and estradiol. Functional FSHR was detected in renal tubular epithelial cells. In vivo, high circulating FSH levels promoted a phenotype of tubulointerstitial fibrosis, characterized by increases in 24‐hr urine protein/creatinine ratio, serum Cr, serum BUN, and ECM deposition. Similar results obtained from cultured HK‐2 cells showed that FSH increased the transcriptional and protein expression of profibrotic mediators (collagen IV, fibronectin, and PAI‐1). This promotion of fibrosis by FSH occurred through the activation of AKT/GSK‐3β/β‐catenin pathway, which could be attenuated by silencing FSHR by siRNA or by LY294002 or MK2206. In addition, FSH‐stimulated HK‐2 cells secreted IL‐8, which promoted macrophage migration to exacerbate tubulointerstitial fibrosis. These results revealed a previously unknown effect of FSH on kidney injury, which may offer a critical insight into the development of CKD in aging postmenopausal women.

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“…IL-8 is secreted by Th1 cells, IL-8 is secreted by Th1 cells and mediate cytotoxic and local inflammationrelated immune response-assisted antibody production. Its main biological functions are to activate neutrophils and promote neutrophil lysosomal enzyme activity and phagocytosis (Meniailo et al, 2018). IL-25 is a new member of the IL-17 family.…”

Section: Mirnas and Mg-related Immune Cells And Cytokinesmentioning

confidence: 99%

Emerging Roles of Dysregulated MicroRNAs in Myasthenia Gravis

Wang

Zhang

2020

Front. Neurosci.

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Myasthenia gravis (MG) is a rare acquired autoimmune neuromuscular disease. Autoantibodies, cellular immunity, complement, and cytokines are involved in the pathogenesis of MG. It is characterized by the dysfunction of neuromuscular junction transmission and skeletal muscle weakness. MicroRNAs (miRNAs) are non-coding small molecule ribonucleic acids that regulate various biological processes (e.g., development, differentiation, and immunity) at the transcriptional and post-transcriptional levels of gene expression. miRNAs play an important regulatory role in the pathogenesis of autoimmune diseases, including MG. In recent studies, the functional mechanisms underlying the role of miRNAs in the pathogenesis of MG have received increasing attention. miRNAs are highly stable and have high specificity in peripheral body fluids. Therefore, the miRNAs in body fluids may represent promising biomarkers for determining the prognosis of MG and the efficacy of treatment. This article reviews the role of miRNAs in the pathogenesis of MG, highlights the potential of miRNAs as new biomarkers for the diagnosis of MG, and deepens our understanding of disease processes.

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Interleukin-8 favors pro-inflammatory activity of human monocytes/macrophages

Cited by 53 publications

References 22 publications

BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper-activation of monocytes from patients with cardiovascular disease and type 2 diabetes

BET protein inhibitor apabetalone (RVX-208) suppresses pro-inflammatory hyper-activation of monocytes from patients with cardiovascular disease and type 2 diabetes

Follicle‐stimulating hormone promotes renal tubulointerstitial fibrosis in aging women via the AKT/GSK‐3β/β‐catenin pathway

Emerging Roles of Dysregulated MicroRNAs in Myasthenia Gravis

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