136: Heat shock proteins and inflammation-induced preterm birth

Abstract

Heat shock proteins (HSP) have been suggested to be critical players in inflammatory disease states by binding to Toll-like receptor-4(TLR-4) as endogenous ligands. HSPs are released from cells in response to stress and function as regulators of the innate immune response. Limited obstetrical studies suggest that HSPs may have a mechanistic role in preterm birth (PTB) or may be promising biomarkers. These studies sought to determine 1) the regulation of HSP during pregnancy and in the setting of inflammation-induced PTB and 2) the validity of HSP as a potential non-invasive biomarker using a mouse model of PTB. 2 sets of experiments were performed. 1) Cervical (CX) and uterine (UT) tissue was harvested from CD-1 non-pregnant (NP) and pregnant mice on E15, E17, E19 (n=3-6 mice/group). 2) On E15, dams were randomized to intrauterine infusion of saline or lipopolysaccharide (LPS)(N=5-6/group). 6 hrs later, maternal serum (MS), CX and UT were collected for QPCR and ELISA for evaluatoin of HSP 70. HSP 70 levels were undetectable in saline-exposed dams in maternal serum. While HSP 70 was increased in LPS-exposed, variability between dams was pronounced. SEE TABLETabled 1E15 / NPE15 / NPE15 LPS / E15E15 LPS / E15CervixUterusCervixUterusHSP60−9.4−1.5−1.61.6HSP70−10.22.1−2.51.1HSP90−5.91.7−1.61.3 Open table in a new tab HSPs do not appear to be critically involved in the pathogenesis of PTB. Down-regulation of HSPs in the CX during normal pregnancy could be a protective mechanism against preterm cervical ripening by preventing endogenous ligands from activating TLRs.