TY - JOUR T1 - Lipopolysaccharide- and Lipoteichoic Acid-mediated Pro-inflammatory Cytokine Production and Modulation of TLR2, TLR4 and MyD88 Expression in Human Endometrial Cells T2 - Journal of Reproduction & Infertility JT - Journal of Reproduction & Infertility SP - 072 EP - 82 VL - 16 IS - 2 PY - 2015 SN - 2251-676X L1 - https://www.jri.ir/documents/fullpaper/en/621.pdf L2 - https://www.jri.ir/article/621 UR - https://www.jri.ir/en/currentissue.aspx?id=63 PB - Avicenna Research Institute AU - Rashidi, Nesa AU - Mirahmadian, Mahroo AU - Jeddi-Tehrani, Mahmood AU - Rezania, Simin AU - Ghasemi, Jamileh AU - Kazemnejad, Somaieh AU - Mirzadegan, Ebrahim AU - Vafaei, Sedigheh AU - Kashanian, Maryam AU - Rasoulzadeh, Zahra AU - Zarnani, Amir Hassan AB -

Background: Toll-like receptor (TLR)-mediated inflammatory processes are supposed to be involved in pathophysiology of spontaneous abortion and preterm labor. Here, we investigated functional responses of human endometrial stromal cells (ESCs) and whole endometrial cells (WECs) to lipopolysaccharide (LPS) and lipoteichoic acid (LTA).
Methods: Endometrial tissues were obtained from 15 cycling women who underwent laparoscopic tubal ligation. Modulation of TLR2, TLR4 and MyD88 expression and pro-duction of pro-inflammatory cytokines by WECs and ESCs in response to LPS and LTA were assessed.
Results: WECs and ESCs expressed significant levels of TLR4 and MyD88 transcripts but, unlike WECs, ESCs failed to express TLR2 gene. Regardless of positive results of Western blotting, ESCs did not express TLR4 at their surface as judged by flow cytometry. Immunofluorescent staining revealed intracellular localization of TLR4 with predominant perinuclear pattern. LPS stimulation marginally increased TLR4 gene ex-pression in both cell types, whereas such treatment significantly upregulated MyD88 gene expression after 8 hr (p<0.05). At the protein level, however, LPS activation significantly increased TLR4 expression by ESCs (p<0.05).  LTA stimulation of WECs was accompanied with non-significant increase of TLR2 and MyD88 transcripts. LPS and LTA stimulation of WECs caused significant production of IL-6 and IL-8 in a dose-dependent manner (p<0.05). Similarly, ESCs produced significant amounts of IL-6, IL-8 and also TNF-α in response to LPS activation (p<0.05).
Conclusion: Our results provided further evidence of initiation of inflammatory processes following endometrial TLR activation by bacterial components which could potentially be harmful to developing fetus.

CY - Tehran, Iran LA - English