GBP5 exacerbates rosacea‐like skin inflammation by skewing macrophage polarization towards M1 phenotype through the NF‐κB signalling pathway

Abstract

Background: Rosacea is a chronic inflammatory skin disease with increased macrophage infiltration. However, the molecular mechanism remains unclear. Objectives: To determine the significance of macrophage infiltration, and the correlation between Guanylate-binding protein 5 (GBP5) and polarization of macrophages in rosacea-like inflammation. Methods: Here we tested the hypothesis that Guanylate-binding protein 5 (GBP5) aggravates rosacea-like skin inflammation by promoting the polarization of the M1 macrophages through the NF-κB signalling pathway. We depleted macrophage by injecting clodronate-containing liposomes. We next explored the association between GBP5 and macrophage in rosacea tissue through transcriptome analysis and immunofluorescence analysis. We evaluated the severity of rosacea-like skin inflammation when BALB/c mice were injected with GBP5 siRNA intradermally daily for three consecutive days. At last, to study the causality of knocking down GBP5-blunted M1 macrophage polarization, THP-1 cell was treated with GBP5 siRNA. Results: Macrophage depletion ameliorated rosacea-like skin inflammation in mice, implying the important role of macrophages in rosacea. Based on the transcriptome analysis, Guanylate-binding protein 5 (GBP5) was identified as hub gene that was associated with macrophage infiltration in rosacea. Next, we found that GBP5 expression was significantly upregulated in rosacea tissues and positively correlated with macrophage infiltration, the immunofluorescence analysis revealed the colocalization between GBP5 and macrophages. In vivo, silencing of GBP5 attenuated rosacea-like skin inflammation in the LL-37-induced mouse model and suppressed the expression of M1 signature genes such as IL-6, iNOS and TNF-a. In vitro, knocking down GBP5 significantly blunted the polarization of the M1 macrophages partly by repressing the activation of the NF-κB signalling pathways. Conclusions: Together, our study revealed the important role of macrophages in rosacea and identified GBP5 as a key regulator of rosacea by inducing M1 macrophage polarization via NF-κB signalling pathways.

Neonatal IL-4 Over-Exposure is Accompanied by Macrophage Accumulation in Dura Mater After Instant Anti-inflammatory Cytokine Response in CSF

“…Therefore, macrophages in dura mater were observed at P42 when pro-inflammatory effect appeared in the CSF and hippocampus in IL-4 group. NF-κB signaling is the major pathway by which macrophage polarize towards M1 phenotype and F4/80 + /NF-κB + cells represent pro-inflammatory activation profile of macrophages (Wu et al 2022a ; Wang et al 2014 ; Zhou et al 2023 ). So we also observed the expression of NF-κB in dural macrophages by double labeling using immunofluorescence staining.…”

RNA-seq analysis reveals modulation of inflammatory pathways by an enriched-triterpene natural extract in mouse and human macrophage cell lines

“…OBE100 inhibits the expression of NFKBIZ, OSM, GBP5, IL1A, and IL6 genes in both human and mouse cells. NFKBIZ, a member of the ankyrin-repeat family and induced by lipopolysaccharide (LPS), OSM, a member of the IL-6 family of cytokines, and GBP5, a member of the dynamin superfamily of GTPases, are involved in the induction of inflammatory genes, including IL6 and IL1A [ [43] , [44] , [45] , [46] ]. IL6 encodes a cytokine that functions in inflammation and the maturation of B cells, and IL1A mediates the activation of NF-kappa B and the three MAPK pathways p38, p42/p44, and JNK pathways [ 47 , 48 ].…”

OPN promotes pro-inflammatory cytokine expression via ERK/JNK pathway and M1 macrophage polarization in Rosacea

“…It was found that M1 macrophage polarization promoted rosacea in ammation [17,30]. M1 macrophage polarization in rosacea may be the result of multiple factors.…”