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PubMed RSS Feed - -GBP5 exacerbates rosacea-like skin inflammation by skewing macrophage polarization towards M1 phenotype through the NF-KB signaling pathway


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J Eur Acad Dermatol Venereol. 2022 Nov 11. doi: 10.1111/jdv.18725. Online ahead of print.


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 correlation between Guanylate binding protein 5 (GBP5) and polarization of macrophages in rosacea-like inflammation.

METHODS: Here we tested hypothesis that Guanylate binding protein 5 (GBP5) aggravate rosacea-like skin inflammation by promoting the polarization of the M1 macrophages through the NF-κB signaling 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 was injected GBP5 siRNA intradermally daily for three consecutive days. At last, to study the causality of knocking down GBP5-blunted M1 macrophages 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 the rosacea. Basing on transcriptome analysis, Guanylate binding protein 5 (GBP5) was identified as hub genes that was associated with the macrophage infiltration in rosacea. Next, we found that GBP5 expression was significantly upregulated in rosacea tissues and positively correlated with the 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 signaling 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 macrophages polarization via NF-κB signaling pathways.

PMID:36367676 | DOI:10.1111/jdv.18725

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