Secretory component (SC or poly-Ig receptor) plays a key role in mucosal external body fluids. The aim of this study was to elucidate the molecular events underlying IFN-gamma-dependent up-regulation of SC. Using a human SC cDNA clone isolated by our laboratory, we found that IFN-gamma up-regulated SC mRNA levels in a time- and concentration-dependent manner. Moreover, in situ hybridization showed a striking increase of SC mRNA-positive HT-29 cells after IFN-gamma treatment. Inhibition with 5,6-dichloro-1-beta-ribofuranosyl-benzimidazole (DRB) indicated a half-life for IFN-gamma-induced SC mRNA of approximately 1 h. Cycloheximide (CHX) abolished the IFN-gamma-induced accumulation of SC mRNA in a reversible manner; the time-course suggested that de novo synthesis of protein factor(s) with a turnover time shorter than 6 h was required for accumulation of SC message. IFN-gamma-stimulated up-regulation of SC expression therefore appears to depend on molecular events similar to those taking place for the activation of several other genes in the Ig supergene family.