Content area

Full Text

Valeria Manganelli [1] and Antonella Capozzi [1] and Simona Truglia [2] and Cristiano Alessandri [2] and Emanuela Lococo [1] and Tina Garofalo [1] and Caterina De Carolis [3] and Fabrizio Conti [2] and Guido Valesini [2] and Maurizio Sorice [1] and Agostina Longo [1] and Roberta Misasi [1]

Academic Editor: Jacek Tabarkiewicz

1, Department of Experimental Medicine, Sapienza University, Rome, Italy, uniroma1.it

2, Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza University, Rome, Italy, uniroma1.it

3, Gynecology and Obstetrics, “San Giovanni Addolorata” Hospital, Rome, Italy, hsangiovanni.roma.it

Received May 26, 2017; Revised Nov 7, 2017; Accepted Nov 14, 2017

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

Inflammatory processes are implicated in every step of fertility, including early pregnancy (implantation and decidualization) [1]. However, recent evidence revealed that inflammatory triggers can lead to adverse pregnancy outcomes, such as preterm birth [2].

Understanding the mechanisms by which inflammation is untimely triggered in the uterus is fundamental to developing effective therapeutics to improve fertility and decrease poor obstetrical outcomes.

Recent studies have highlighted a close association between high mobility group box 1 (HMGB1), chronic inflammation, and autoimmune diseases [3, 4]. HMGB1 is a 30 kDa nuclear protein which organizes DNA and regulates transcription; it has been shown to play an important role in helping the recombination activating gene (RAG) endonuclease to form a complex during VDJ recombination. In addition, it was also found in cytosol, mitochondria, and cell plasma membrane, where it can be released to the extracellular milieu [5, 6]. In particular, during inflammation, HMGB1 may be secreted by immune cells, such as macrophages, monocytes, and dendritic cells. This molecule shows all the typical features of alarmins and plays a pivotal role in inducing and enhancing immune cell function, as well as in tissue injury and repair [7, 8]. HMGB1 can interact with Toll-like receptors (TLRs) and activates cells through multiple surface receptors, including Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), the receptor for advanced glycation end-products (RAGE), leading to an upregulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), with production and release of cytokines, stimulating reactive oxygen...

Show less