Figure 2.

Damage‐associated molecular patterns (DAMPs), pathogen‐associated molecular patterns (PAMPs) and endogenous TLR4 activators in gestational tissues during preterm labour. An array of TLR4 ligands and activators accumulate in fetal and maternal tissues where they drive an amplifying inflammatory cascade of cytokine expression and leucocyte infiltration. TLR4 ligands including LPS and other PAMPs of microbial origin are produced by microbial infection. Endogenous DAMPs produced during sterile tissue insult or injury can also activate TLR4. These DAMPs include HSP70 and HMGB1 released from fetal membranes and PAF and SP‐A released from fetal lungs. DAMPs can also be released after microbial infection. TLR4 is abundantly expressed by leucocytes and other cell lineages in fetal membranes, uterine decidua and myometrium, and cervical tissues. TLR4 ligands can be transmitted from amniotic fluid into the myometrium and cervix, to amplify inflammatory activation and ultimately cause uterine contractions, cervical dilation and delivery of the fetus.