Intrauterine infection and preterm labor

Overview of proposed pathways of infectious and non-infectious labor. AP-1, activator protein 1; CCL5, chemokine (C-C motif) ligand 5; dsRNA, double-stranded RNA; IL, interleukin; LMW-HA, low molecular weight hyaluronan; LPS, lipopolysaccharide; LTA, lipoteichoic acid; NFκB, nuclear factor κB; PAF, platelet-activating factor; PGN, peptidoglycan; STAT, signal transducers and activators of transcription; TNF, tumor necrosis factor.

Synergy between toll-like receptor (TLR)-2 and TLR3 activation. (a) In vivo: preterm delivery rates in day-14.5 pregnant CD-1 mice following intrauterine administration of peptidoglycan (PGN) (TLR2 agonist) and/or polyinosinic:cytidylic acid [poly(I:C)] (TLR3 agonist). Preterm delivery was defined as delivery of at least one pup within 48 h (all deliveries occurred in <36 h). P-Values are by Fisher’s exact test. (b) In vitro: RAW 264.7 cells were stimulated with either phosphate-buffered saline, PGN (1 μg/mL), poly(I:C) (10 μg/mL) or both PGN and poly(I:C) for 5 h. Real-time polymerase chain reaction was performed for interleukin (IL)-1β and normalized to the housekeeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH). P-Value was calculated for all four treatments simultaneously by analysis of variance. n = 3 replicates per condition. Depicted is a representative example from among three repeat experiments. Similar results were obtained for tumor necrosis factor-α, nitric oxid synthase 2 and chemokine (C-C motif) ligand 5 (CCL5) (not shown).⁶ Modified from Ilievski and Hirsch.⁶