Functional Screening of TLRs in Human Amniotic Epithelial Cells

Intrauterine infection is a major cause of spontaneous preterm birth. Amniotic epithelial cells represent the first line of defense against intra-amniotic bacteria. We hypothesize that this epithelial cell barrier is able to recognize and respond to pathogens through the function of TLRs, which are crucial regulators of the innate immune system. In this study, we describe the expression of transcripts for TLR1-TLR10 in human amniotic epithelial cells. We show that amniotic epithelial cells express functional TLR5, TLR6/2, and TLR4. Activation by TLR5 and TLR6/2 agonists produces IL-6 and IL-8, concomitantly with the activation of NF-kappa B signaling pathway, matrix metalloproteinase-9 induction, and PTGS2 expression. In contrast, TLR4 activation reduced amniotic epithelial cell viability and induced cell apoptosis evidenced by an elevated Bax/Bcl-2 ratio and cleavage of caspase-3. These data suggest specific TLR-mediated functions in human amniotic epithelial cells for initiating different immune responses, which ultimately may lead to preterm birth. The Journal of Immunology, 2011, 187: 2766-2774.