The purpose of the present study was to investigate the role of estrogen in modulating TNF-α responses during Dr+ E.coli infection in mIMCD-3 cells. E2 and ER antagonist ICI-182780 pre-treated mIMCD-3 cells were infected with Dr+ E.coli for 2 and 8 hours. TNF-α and DAF expression at mRNA levels were determined by quantitative Real-time RT-PCR and secreted protein quantified by ELISA. E2 modulated TNF-α mRNA levels at both time points in Dr+ E.coli infected mIMCD-3 cells. ICI-182, 780 and E2 co-treatment of cells reversed the observed E2 effects on TNF-α mRNA. TNF-α mRNA increase in DR+ E.coli infected cells also coincided with down-regulation of DAF mRNA. Significant reversal of DAF mRNA levels was induced by co-treatment of the cells with E2 and ICI. Thus, E2 mediates protective effects against Dr+ E.coli invasion in mIMCD-3 cells by modulating TNF-α and DAF production.Department of Biochemistry and Molecular Biolog