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Background: Secretory component (SC) is the extracellular component of the polymeric immunoglobulin receptor (pIgR) that functions as a receptor for externally secreted polymeric immunoglobulins such as secretory IgA. SC expression is regulated by a signaling pathway involving TNF-a. Methods: Caco-2 cells were cotreated with TNF-α plus either Wortmannin, which inhibits PI3K, or Rapamycin, which inhibits mTOR. The expression of SC and pIgR mRNA were assessed by immunocytochemistry, Western blotting, and Quantitative real-time PCR. Results: Wortmannin and Rapamycin decreased the fraction of cells expressing SC, as well as the total expression of SC protein and pIgR mRNA. Conclusions: TNF-α regulation of SC expression is mediated through a PI3K/AKT/mTOR signaling pathway in Caco-2 cells.