Keratinocyte Growth Factor Stimulates Macrophage Inflammatory Protein 3α and Keratinocyte-derived Chemokine Secretion by Mouse Uterine Epithelial Cells

Problem Communication between uterine epithelial cells and the underlying stromal fibroblasts is critical for proper endometrial function. Stromal fibroblast-derived growth factors have been shown to regulate epithelial immune functions. The purpose of this study was to determine whether keratinocyte growth factor (KGF) regulates uterine epithelial cell chemokine and antimicrobial secretion. Method of study Uterine epithelial cells were isolated from Balb/c mice and cultured in either 96-well plates or transwell inserts. Epithelial cells were treated with KGF, epidermal growth factor (EGF), or hepatocyte growth factor (HGF). Macrophage inflammatory protein 3 alpha (MIP3 alpha) and keratinocyte-derived chemokine (KC) levels were measured by ELISA. Results Keratinocyte growth factor stimulated the secretion of MIP3 alpha and KC. The effects on MIP3 alpha by KGF were specific because EGF and HGF had no effect. In contrast, KGF, EGF, and HGF had similar effects on KC. Furthermore, KGF administered to the apical side of epithelial cells had no effect on MIP3 alpha or KC secretion, indicating that the KGF receptor is located on the basolateral surface of uterine epithelial cells. Conclusion We demonstrate that KGF plays a role in uterine epithelial cell secretion of MIP3 alpha and KC, key immune mediators involved in the protection of mucosal surfaces in the female reproductive tract.