IL-1β/NF-κB signaling inhibits IGF-1 production via let-7f-5p in dendritic epidermal T cells

Abstract

Dendritic epidermal T cells (DETCs) are the main source of insulin‐like growth factor‐1 (IGF‐1) in epidermal tissue, which promote re‐epithelialization and wound healing. In refractory wounds, IL‐1β has been shown to activate NF‐κB and suppress IGF‐1 expression in DETCs. Nevertheless, the underlying mechanisms remain unclear. In this study, chromatin immunoprecipitation analysis revealed that IL‐1β did not inhibit NF‐κB binding to IGF‐1 promoter, indicating that IL‐1β/NF‐κB may suppress IGF‐1 expression by alternative mechanisms. MiRNAs negatively regulate gene expression predominantly by base pairing to the 3′ untranslation region (UTR) of target mRNAs. Let‐7f‐5p, miR‐1a‐3p, and miR‐98‐5p have been identified as IGF‐1‐specific miRNAs that can bind directly to the 3′UTR of IGF‐1 mRNA and dysregulate IGF‐1 mRNA and protein levels. In IL‐1β‐treated epidermis around wounds or DETCs in vitro, NF‐κB promoted the expression of let‐7f‐5p, and IGF‐1 expression was impeded via NF‐κB/let‐7f‐5p pathway. As pre‐let‐7f‐5p, let‐7f‐1 is located in the 3′UTR of LOC118568094, and let‐7f‐2 is located in the intron of HUWE1. We discovered that NF‐κB p65 bound to the promoters of LOC118568094 and HUWE1 to accelerate let‐7f‐5p expression, but NF‐κB p65 did not affect the methylation levels of LOC118568094 and HUWE1 CpG islands. Injections of Let‐7f‐5p antagomir into IL‐1β‐treated and ischemic wound margins restored IGF‐1 secretion in DETCs and promoted wound healing. In conclusion, we demonstrated that NF‐κB signaling pathway activated by IL‐1β could increase let‐7f‐5p expression to inhibit IGF‐1 production in DETCs and delay wound healing. And let‐7f‐5p antagomir utilized in wound margin could effectively promote refractory wound healing.

Time-dependent effect of inflammation on the gene expression of pro-inflammatory cytokines and their receptors at the different levels of the somatotropic axis in ewe

“…These increases in local synthesis of pro-inflammatory cytokines may significantly influence the secretion of IGF1. It was found that IL1B inhibits IGF1 production in dendritic epidermal T cells (Li et al, 2022). Previous studies also demonstrated that IL6 inhibits the secretion of IGF1 and that IL6 overproduction is a mechanism implicated in IGF1 downregulation (Barbieri et al, 2003).…”

MCC950 Ameliorates Acute Exogenous Lipoid Pneumonia Induced by Sewing Machine Oil in Ratsviathe NF-κB/NLRP3 Inflammasome Pathway

“…It was widely known that NF-ĸB plays a role upstream of NLRP3 (34). Whereas, over-expressed NLRP3 also contributes to the expression of IL-1β and IL-18, and many studies showed that IL-1β can stimulate the activation of NF-ĸB signalling pathway through a feedback loop (35)(36)(37)(38). The up-regulated IL-1β production might lead to the lung injury.…”