Abstract

BackgroundTo investigate the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK) on the production of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, prostaglandin E2 and F2α induced by IL-1β in endometrial stromal cells (ESCs) following treatment with 5-aminoimidazole-4- carboxamide ribonucleoside (AICAR).MethodsEndometrial specimens were obtained and cultured. We examined the effects of IL-1β, IL-1 ra and AICAR on the production of IL-8, MCP-1, PGE2 and PGF2α in human ESCs. The phosphorylations of AMPK, IκB, 4EBP-1, p70S6K and S6 ribosomal protein were analyzed by Western immunoblotting.ResultsFollowing stimulation by IL-1β, the production of IL-8, MCP-1, PGE2 and PGF2α showed significant increases, and these increases were suppressed by AICAR. The expression of cyclooxygenase-2 (COX-2) induced by IL-1β and suppressed by AICAR. The phosphorylation of IκB, 4EBP-1, p70S6K and S6 ribosomal protein were inhibited via an AMPK-dependent signal transduction.ConclusionsThe production of IL-8, MCP-1, PGE2 and PGF2α induced by IL-1β in ESCs were involved in the negative regulatory mechanisms of AMPK. The substances that activate AMPK may be promising agents for the treatment of pathological problems such as dysmenorrhea.

Highlights

  • Human endometrial stromal cells (ESCs) undergo morphologic and functional changes to provide the most suitable conditions for embryo implantation, which is regulated by several cytokines [1], polypeptide growth factors [2], steroid hormones, and eicosanoids including platelet-activating factor and prostaglandins (PGs) [3]

  • Adenosine monophosphate-activated protein kinase (AMPK) phosphorylation was induced by AICARTo elucidate the role of AMPK in the ESCs, we examined the effects of aminoimidazole-4- carboxamide ribonucleoside (AICAR) on the phosphorylation of AMPK

  • We found that 1 mM AICAR activated AMPK time-dependently compared to the controls (Fig. 1A, B)

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Summary

Introduction

Human endometrial stromal cells (ESCs) undergo morphologic and functional changes to provide the most suitable conditions for embryo implantation, which is regulated by several cytokines [1], polypeptide growth factors [2], steroid hormones, and eicosanoids including platelet-activating factor and prostaglandins (PGs) [3]. The adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an energy-sensing enzyme with a heterotrimeric complex that is believed to be implicated in the regulation of energy metabolism at the intracellular and whole-organ levels [6,7,8]. It is suspected that 5-aminoimidazole-4-carboxamide ribonucleoside (ZMP) is converted from AICAR by adenosine kinase in the cells. To investigate the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK) on the production of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, prostaglandin E2 and F2α induced by IL-1β in endometrial stromal cells (ESCs) following treatment with 5-aminoimidazole-4- carboxamide ribonucleoside (AICAR)

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