Residual concentrations of erythromycin in food could result in gastrointestinal tract exposure that potentially poses a health-hazard to the consumer, affecting intestinal epithelial permeability, barrier function, microbiota composition, and antimicrobial resistance. We investigated the effects of erythromycin after acute (48 h single treatment with 0.03 μg/mL to 300 μg/mL) or chronic (repeated treatment with 0.3 µg/mL and 300 µg/mL erythromycin for five days) exposures on the permeability of human colonic epithelial cells, a model that mimics a susceptible intestinal surface devoid of commensal microbiota. Transepithelial electrical resistance (TER) measurements indicated that erythromycin above 0.3 µg/mL may compromise the epithelial barrier. Acute exposure increased cytotoxicity, while chronic exposure decreased the cytotoxicity. Quantitative PCR analysis revealed that only ICAM1 (intercellular adhesion molecule 1) was up-regulated during 0.3 μg/mL acute-exposure, while ICAM1, JAM3 (junctional adhesion molecule 3), and ITGA8 (integrin alpha 8), were over-expressed in the 300 μg/mL acute treatment group. However, during chronic exposure, no change in the mRNA expression was observed at 0.3 μg/mL, and only ICAM2 was significantly up-regulated after 300 μg/mL. ICAM1 and ICAM2 are known to be involved in the formation of extracellular matrices. These gene expression changes may be related to the immunoregulatory activity of erythromycin, or a compensatory mechanism of the epithelial cells to overcome the distress caused by erythromycin due to increased permeability.
Keywords: acute or multiple dose exposure; epithelial cell barrier function; erythromycin; gene expression; permeability; single dose exposure.