ZNF580 – a brake on Interleukin-6

Abstract

BackgroundZinc finger protein 580 (ZNF580) was reported to modulate angiogenesis, endothelial homeostasis and blood pressure control. ZNF580 regulated genes include VEGF-A and IL-8. However, it is unknown if ZNF580 could play a role during inflammation. The aim of this study was to find out if ZNF580 affects the expression of IL-6, if it occurs in monocytic cells and responds to inflammatory mediators.ResultsOverexpression of ZNF580 reduced LPS-induced promotor activity of IL-6. Consistently, overexpression of ZNF580 reduced by half the LPS-induced expression of IL-6. ZNF580 was strongly expressed in the nucleus of MonoMac6, a human monocytic cell line. LPS-stimulated IL-6 secretion increased when ZNF580 was suppressed with siRNA. After stimulation of MonoMac6 with LPS for 24 h, ZNF580 negatively correlated with the amount of secreted IL-6. In response to LPS, ZNF580 was increased within the first 8 h, followed by a marked decrease after 16 h. This decrease coincided with sustained IL-6 production.ConclusionThis study demonstrated that ZNF580 inhibits LPS-induced expression of IL-6. ZNF580 was highly expressed in monocytic cells and therefore may contribute to the modulation of its IL-6 production, at least in response to LPS. This suggests cooperation between ZNF580 and NFκB, which could play a role during sepsis.

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

“…Additionally, among common DEGs in stage I-II endometriosis, several of them are relative to inflammatory and/or infectious process. ZNF580 is potentially involved in the modulation of inflammatory process 141 ; DCAF15 is potentially involved in the immune surveillance 142 ; BANF1 is involved in the immunity against integration of foreign DNA and response to DNA damage 143 , and it is required to maintain undifferentiated phenotype of the stem cells 144 ; HECTD3 is associated to the modulation of host defense against infection 145 ; SSC5D, which is a soluble receptor produced by macrophages, T cells, and epithelial cells from placenta, is upregulated on infection and it has capacity to interact with bacteria 146 ; TEFB has a role in the autophagy and in the regulation of inflammasome 147 ; CD74 plays a role in the macrophage recruitment, adhesion and migration 148 . Despite the debatable utility of the biomarkers as noninvasive tool to diagnosis endometriosis 149,150 , these differences in transcript levels should be investigated further, at least as a driver to understand its pathophysiology.…”

TMEM147 is a novel biomarker for diagnosis and prognosis of hepatocellular carcinoma

“…ZNF146 was reported to be targeting to distinct sites within LINE-1 sequences at thousands of locations in the genome and to promote tumorigenesis of HCC, gastric cancer, and colorectal cancer ( Ma et al, 2020 ; Bao et al, 2021 ; Zhu et al, 2021 ; Creamer et al, 2022 ). ZNF580 was reported to regulate the gene expression of VEGF-A, IL-8, MMP2, and SMAD2 and is involved in angiogenesis, endothelial inflammation, and cell migration and proliferation ( Sun et al, 2010 ; Stenzel et al, 2018 ). These 5 proteins were predicted to be transcription factors for TMEM147, indicating a possible mechanism that mediates the transcriptional upregulation of TMEM147 in HCC.…”

Zfp580 Regulates Paracrine and Endocrine Igf1 and Igfbp3 Differently in the Brain and Blood After a Murine Stroke

“…In vitro , Zfp580 suppressed Igf1 and Igfbp3 expression in microvascular cerebral endothelial cells. Zfp580 is known to act on inflammatory and angiogenetic signaling pathways ( Sun et al, 2010 ; Hoffmann et al, 2011 ; Luo et al, 2014 ; Stenzel et al, 2018 ). We identified growth hormone pathways as a new signaling pathway that is influenced by Zfp580.…”

“…Zincfinger protein 580 (Zfp580) is a transcription factor that is involved in inflammation, angiogenesis and signaling triggered by hypoxia ( Sun et al, 2010 ; Hoffmann et al, 2011 ; Meng et al, 2014 ; Stenzel et al, 2018 ). As recently demonstrated, Zfp580 may play a role in Igfbp3 regulation ( Yin et al, 2022 ).…”