Proteolytic dysfunction in bovine digital dermatitis caused by Treponema spp. and the therapeutic use of non-antimicrobial matrix metalloproteinase inhibitors.

ABSTRACT: Digital dermatitis (DD) is a painful hoof disease in cattle, closely linked to Treponema spp., for which the pathogenesis remains poorly understood and effective treatments are lacking. This study identifies a persistent pro-inflammatory proteomic signature in untreated, non-healing active DD lesions in the foot skin of cattle, characterized by increased immune cell infiltration and elevated matrix metalloproteinase (MMP) activity. Treatment of active DD lesions with CMC2.24, a non-antibiotic MMP inhibitor, maintains the lesions in an M2 stage in most cases; however, it reduces histological dermatitis, lowering reactive oxygen species (ROS) levels and downregulating proteomic keratinization pathways. Mechanistically, CMC2.24 dampens inflammatory IL-1β cell responses in bovine macrophages e

SUBMITTER: Lahiri P 

PROVIDER: S-EPMC12572248 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature