PMID- 12516629 OWN - NLM STAT- MEDLINE DCOM- 20030416 LR - 20190922 IS - 1046-7408 (Print) IS - 1046-7408 (Linking) VI - 48 IP - 4 DP - 2002 Oct TI - IL-18 is present at the maternal-fetal interface and enhances cytotoxic activity of decidual lymphocytes. PG - 191-200 AB - PROBLEM: Perforin expressing uterine natural killer (uNK) cells are under complex cytokine influence. The aim of the study was to investigate the presence and role of interleukin (IL)-18 on NK cytolytic potential at maternal-fetal (M-F) interface. METHOD OF STUDY: Peripheral blood cells and decidual tissue were obtained from elective pregnancy termination of normal human 6-10-week-old pregnancies. Perforin expression and cytolytic activity of peripheral blood (PBL) and decidual lymphocytes (DL) were analyzed by flow cytometry. IL-18 positive decidual adherent cells (DAC) were detected by the same method. Interleukin-18 and IL-18 receptor (IL-18R) expression on the trophoblastic cells was detected by immunohistology using biotinylated anti-IL-18 and IL-18R monoclonal antibodies. RESULTS: The IL-18 added in a dose of 10 ng/mL up-regulates perforin expression and cytolytic activity of DL. Simultaneous stimulation with IL-18 and IL-12 enhanced DL cytolytic activity, while IL-18 combined with IL-10 or IL-15 did not show this effect. Cytolytic activity of PBL was up-regulated by IL-18 as well, and this effect was enhanced by the addition of IL-12 and IL-15. Interleukin-18 did not affect perforin-protein expression in cultured PBL. Approximately 20% of DAC were IL-18 positive and these cells were mostly human leukocyte antigen (HLA)-DR negative. IL-18R positive cells were found on syncytiotrophoblast cell layer, interstitial tissue cells of villi and fetal blood cells. There was no detectable IL-18 staining on trophoblast cell layer on villi, but strong staining of fetal blood cells in villous vessels. CONCLUSION: These are first results showing IL-18R expression, but not IL-18 expression on villous trophoblastic cells, as well as enhancement of perforin expression and NK cytolytic potential of DL under the influence of IL-18. IL-18 in concert with other cytokines and hormones could play an important role in the regulation of cytolytic potential of first trimester pregnancy decidual and peripheral blood NK cells. FAU - Tokmadzic, Vlatka S AU - Tokmadzic VS AD - Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia. FAU - Tsuji, Yoshiyuki AU - Tsuji Y FAU - Bogovic, Tatjana AU - Bogovic T FAU - Laskarin, Gordana AU - Laskarin G FAU - Cupurdija, Kristijan AU - Cupurdija K FAU - Strbo, Natasa AU - Strbo N FAU - Koyama, Koji AU - Koyama K FAU - Okamura, Haruki AU - Okamura H FAU - Podack, Eckhard R AU - Podack ER FAU - Rukavina, Daniel AU - Rukavina D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Denmark TA - Am J Reprod Immunol JT - American journal of reproductive immunology (New York, N.Y. : 1989) JID - 8912860 RN - 0 (Interleukin-18) RN - 0 (Interleukins) RN - 0 (Membrane Glycoproteins) RN - 0 (Pore Forming Cytotoxic Proteins) RN - 126465-35-8 (Perforin) SB - IM MH - Adult MH - Chorionic Villi/metabolism MH - Decidua/*metabolism MH - Female MH - Flow Cytometry MH - Humans MH - Immunohistochemistry MH - Interleukin-18/*metabolism MH - Interleukins/metabolism MH - Killer Cells, Natural/*metabolism MH - Membrane Glycoproteins/metabolism MH - Perforin MH - Pore Forming Cytotoxic Proteins MH - Pregnancy EDAT- 2003/01/09 04:00 MHDA- 2003/04/17 05:00 CRDT- 2003/01/09 04:00 PHST- 2003/01/09 04:00 [pubmed] PHST- 2003/04/17 05:00 [medline] PHST- 2003/01/09 04:00 [entrez] AID - 10.1034/j.1600-0897.2002.01132.x [doi] PST - ppublish SO - Am J Reprod Immunol. 2002 Oct;48(4):191-200. doi: 10.1034/j.1600-0897.2002.01132.x.