RKC-B1 Blocks Activation of NF-κB and NLRP3 Signaling Pathways to Suppress Neuroinflammation in LPS-Stimulated Mice

Abstract

RKC-B1 is a novel fermentation product obtained from the marine micromonospora FIM02-523A. Thus far, there have been few reports about the pharmacological activity of RKC-B1. In our present study, we investigated the anti-neuroinflammatory effects and the possible mechanism of RKC-B1 in LPS-stimulated mice. After treatment with RKC-B1, RNA-seq transcriptome of the cerebral cortex tissue was conducted to find the differentially expressed genes (DEGs). Inflammatory cytokines and proteins were evaluated by ELISA and WB. In RNA-seq analysis, there were 193 genes screened as core genes of RKC-B1 for treatment with neuroinflammation. The significant KEGG enrichment signaling pathways of these core genes were mainly included TNF signaling pathway, IL-17 signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway and others. The corresponding top five KEGG enrichment pathways of three main clusters in PPI network of core genes were closely related to human immune system and immune disease. The results showed that RKC-B1 reduced the levels of pro-inflammatory factors (IL-6, IL-1β, MCP-1, and ICAM-1) and the expression of COX2 in cerebral cortex tissue. Additionally, we found that the anti-neuroinflammation activity of RKC-B1 might be related to suppress activating of NF-κB and NLRP3/cleaved caspase-1 signaling pathways. The current findings suggested that RKC-B1 might be a promising anti-neuroinflammatory agent.

Ovotransferrin Inhibits TNF-α Induced Inflammatory Response in Gastric Epithelial Cells via MAPK and NF-κB Pathway

“…However, the OVT pretreatment repressed the phosphorylation of these proteins, which reflected that the OVT inhibited the activation of NF-κB and MAPK pathways and then resulted in a reduction in the expression of pro-inflammatory cytokines (IL-8, IL-6, IL-1β) and attenuated the inflammatory response. TNF-α, LPS, and other stimulatory signals can trigger NF-κB and MAPK pathways, which primarily control the cytokine secretion and leukocyte recruitment. , Blocking the activation of NF-κB and MAPK pathways may restrain the inflammatory response, which has been demonstrated in vitro and in vivo . ,, In the present study, the NF-κB pathway was inhibited using a p65 inhibitor (which inhibits nuclear translocation of NF-κB p65 but does not affect IκB degradation). ERK, p38, and JNK inhibitors were able to suppress the expression of each of the three subfamilies of MAPK pathways.…”

“…44,45 Blocking the activation of NF-κB and MAPK pathways may restrain the inflammatory response, which has been demonstrated in vitro and in vivo. 26,46,47 In the present study, the NF-κB pathway was inhibited using a p65 inhibitor (which inhibits nuclear translocation of NF-κB p65 but does not affect IκB degradation). ERK, p38, and JNK inhibitors were able to suppress the expression of each of the three subfamilies of MAPK pathways.…”

High-Mobility Group Box 1 Inhibitor BoxA Alleviates Neuroinflammation-Induced Retinal Ganglion Cell Damage in Traumatic Optic Neuropathy

“…To further reveal the mechanism by which HMGB1 regulates inflammatory retinal damage, we examined the expression of NLRP3, ASC, and NF-kB. NF-κB activity was essential for immune responses, and the activation of NF-κB signaling pathways was largely associated with inflammatory diseases [ 36 ]. The inflammasome is a multi-protein complex assembled by PRRs, including NLRP1, NLRP3, and NLRC4 [ 37 ].…”

Proteomics profiles reveal the potential roles of proteins involved in chicken macrophages stimulated by Lipopolysaccharide

“…The classical molecule of LPS is composed of a tripartite structure: Lipid A, the conserved and hydrophobic backbone, which represents the bioactive center and significant toxic effects of gram-negative bacteria (Forsgren and Sjöquist 1966); a core oligosaccharide chain, which is linked to lipid A; and an O side chain or O antigen polysaccharide, which given the abundance of bacterial species (Atkins et al 2008, Goward et al 1993, Laarman et al 2010. Tolllike receptors (TLR), transmembrane proteins on cell surfaces, bind to LPS and trigger inflammatory responses in the host (Liu et al 2021). In mammalian cells, LPS stimulation was performed through protein interactions (Elzawahry et al 2014).…”