S100A8, which increases with age, induces cellular senescence-like changes in bovine oviduct epithelial cells.

Abstract

The oviduct is an essential component in reproduction and oviduct epithelial cells (OECs) secrete various types of cytokine. However, mechanisms of aging and inflammation of OECs are unknown. We previously reported the age-dependent functional changes of bovine OECs such that aged OECs expressed higher levels of inflammatory cytokines. We selected S100A8 and S100A9 as molecules expressed more highly in aged OECs, as candidates to induce age-related changes, and investigated using bovine OECs. The OECs were isolated from bovine oviductal tissues (Aged, more than 120months; Young, between 30 and 50months) and cultured. Aged OECs exhibited higher senescence-associated (SA)-β-gal staining (a biomarker of cellular senescence) and mRNA expression of SA-inflammatory cytokines than young OECs. Cellular senescence occurred in both young and aged OECs upon passaging the cells. Treatment with S100A8, but not S100A9, resulted in the induction of cellular senescence in bovine OECs. Both S100A8 and S100A9 stimulated the secretion of the inflammatory cytokine IL-8 from bovine OECs. S100A8-induced IL-8 secretion was dependent on receptor RAGE, AP-1 activation, and reactive oxygen species production. In addition, S100A8 reduced the content of collagen while inducing the expression of matrix metalloproteinases, suggesting the induction of dysregulation of the extracellular matrix in OECs. We suggest that bovine OECs recognize an excessive increase in age-associated DAMPs, such as S100A8 and S100A9, and that these signals may contribute to chronic oviductal inflammation, resulting in infertility associated with oviductal dysfunction.