HR-1 Mice: A New Inflammatory Acne Mouse Model

ABSTRACT

BACKGROUND: There is no appropriate in vivo animal model that reflects the inflammatory response of human acne. OBJECTIVE: This study investigated the effect of Propionibacterium acnes on the development of inflammatory acne-like lesions in four mouse strains with different degrees of immune response for the development of an optimal mouse model of inflammatory acne. METHODS: Human P. acnes suspensions (10(8) and 10(9) colony forming unit [CFU]/microl) were injected into the backs of HR-1, BALB/c, vitamin D receptor-knockout (VDR k/o), and severe combined immunodeficiency disease mice. Inflammation levels were evaluated two weeks after injection of P. acnes suspensions. In addition, histopathological examination and immunohistochemical staining of the expressions of inflammatory biomarkers (i.e., CD4+/CD8+ T lymphocytes, neutrophils, myeloperoxidase, interleukin-1beta, matrix metalloprotease (MMP)-2, MMP-3, MMP-9, toll-like receptor (TLR)-2, LL-37, and integrin alpha6) were performed on tissue specimens. RESULTS: The HR-1 mouse strain exhibited the most remarkable inflammatory reaction with epithelial proliferation and microcomedone-like cyst formation. HR-1 mice also demonstrated aberrant integrin expression in the epidermis around both inflamed lesions and newly formed microcomedones. These findings were more prominent in the group receiving 10(9) CFU/microl P. acnes than 10(8) CFU/microl. MMP-9 expression in HR-1 mice was also upregulated around the microcomedone-like cysts. Finally, expression levels of TLR-2 and LL-37 were higher in HR-1 and BALB/c mice than the VDR k/o and SCID mice strains. CONCLUSION: P. acnes induces acneiform inflammation with small microcomedones in HR-1 mice. Therefore, the HR-1 mouse strain represents a good candidate for the development of a new inflammatory acne mouse model.