Regenerating gene (REG) I plays important roles in cancer cell biology. The purpose of this study was to determine whether REG I affects cytokine production in cancer cells. We transfected TE-5 and TE-9 squamous esophageal cancer cells with REG I alpha and I beta and examined its effects on cytokine expression. We found that transfecting TE-5 and TE-9 cells with REG I alpha and I beta led to significantly increased expression of interleukin (IL)-6 mRNA and protein, but it had little or no effect on expression of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17A, interferon-gamma, tumor necrosis factor-alpha, granulocyte-colony stimulating factor or transforming growth factor-beta 1. The elevated IL-6 expression seen in REG I alpha transfectants was silenced by small interfering RNA-mediated knockdown. These finding suggest that REG I may act through IL-6 to exert effects on squamous esophageal cancer cell biology. (C) 2009 Elsevier Inc. All rights reserved.