GBP5 Participates In Rosacea By Regulating Macrophage Polarization

Rosacea is a chronic inflammatory skin disease which pathogenesis is still unknown.More and more studies have shown that congenital immune disorder is the key point in rosacea.As one of the important members of skin innate immune system,increased infiltration of macrophages can be detected in the lesions of rosacea.However,the exact biological function and possible underlying mechanisms of macrophages in the pathogenesis of rosacea remain to be explored.Guanylate binding protein 5(GBP5)is a member of dynamin superfamily of GTPases,was reported to be highly expressed in macrophages and involved in macrophages-mediated host defense.However,the role and mechanism of GBP5 in rosacea are currently unclear.Objective: To explore whether GBP5 involved in the pathogenesis of rosacea by affecting macrophages,and to explore its possible molecular mechanism.Methods: We explored the role of macrophages in the pathogenesis of rosacea by removing macrophages from rosacea-like model mice.Xcell and WGCNA methods were used to identify the key gene(GBP5)related to macrophage infiltration in rosacea,and we verified the expression of this gene(GBP5)by q PCR,IHC and IF.Next,we explored whether GBP5 affects macrophage polarization and involves in the pathogenesis of rosacea by knocking down GBP5 in LL37-induced rosacea-like mice,observing the appearance of skin lesions,and detecting histopathology and the expression level of macrophage signature genes.Furthermore,we used transcriptome data to find out the infiltration of macrophages with different polarization types in rosacea and its correlation with GBP5.The vitro study was mainly carried out in human acute monocytic leukemia cell line(THP-1 cells).THP-1 cells were pretreated with Si GBP5,and then polarized with LPS/IFN-γ or IL-4,through detecting the expression of macrophage markers,we investigated the role of GBP5 in the M1 polarization of macrophages.Furthermore,to explore the potential mechanism,we used western blotting to detect the activity of pathways which regulate macrophage polarization.Results:1.Macrophage depletion ameliorated skin inflammation in LL37-induced rosacea-like mice.2.GBP5 was related to macrophages infiltration in rosacea.3.GBP5 expression increased in rosacea skin lesions and was localized with macrophages.4.Inhibition of GBP5 attenuated skin inflammation and M1macrophages-related markers in LL37-induced rosacea-like mice.5.GBP5 participates in M1 polarization of macrophages.6.GBP5 regulates macrophage polarization through NF-k B signal pathway.Conclusion: GBP5 participates in the pathogenesis of rosacea,and can skew macrophage polarization towards M1 phenotype through the NF-k B signaling pathway.Picture 6 frame,0 tables,51 references.