Determination of the role of indomethacin and SP-A on Notch signaling pathways in the cervix and the prevention of preterm labor

Objective: Although the mechanisms are not clear, infection is one of the most important reasons for preterm labor. For this reason, many studies are carried out for treatment. Surfactant A (SP-A) is an endogenous fetal substance with an excellent safety profile for pregnancy. The aim of this study is to identify the potential of indomethacin (IND) which is a prostaglandin inhibitor and of the SP-A as a protective agent for preterm delivery in pregnant women. Method: The dose-effect duration of SP-A and fragments was determined using RAW and RAW Blue cells. The effect of SP-A and Indomethacin was evaluated on a LPS induced surgical model using 14.5 dpc CD-1 mice. Results: After induction with 0.2 ng/ml LPS for 5 hours, expression of IL1β by PCR in RAW cells was evaluated. This effect was suppressed in RAW Blue cells with 20 ug/ml and evaluated by Quanti Blue analysis. The response of the fragments is different depending on the dose and time. Molecular structure after Commassie Blue staining; the monomeric (24 kDa) and dimeric (50-60 kDa) for the full-length SP-A. KINK (22 kDa) was detected as CDM (4 kDa) with GLOB (28 kDa) and PL (2 kDa) with smaller fragments. In the experimental animal model induced by the same dose LPS. The Notch activity in the LPS-mediated preterm delivery group was increased. At the same time, SPA and IND affected the Jag-2 mediated mast cell modulation. Conclusion: When the dose time curve of SP-A and fragments was examined, it was seen that SP-A suppressed the inflammatory response, but SP-A components had different response characteristics. In addition, it was determined that SP-A was important to investigate the linkage of Notch signal in characterizing the molecular mechanism of action. Although more research is needed in this area, this study will be help the design to drug for SP-A. Keywords: SP-A, Indomethacin, Notch, Cervix