Molecular regulators of resolution of inflammation: potential therapeutic targets in the reproductive system

Abstract

Inflammatory processes are central to reproductive events including ovulation, menstruation, implantation and labour, while inflammatory dysregulation is a feature of numerous reproductive pathologies. In recent years, there has been much research into the endogenous mechanisms by which inflammatory reactions are terminated and tissue homoeostasis is restored, a process termed resolution. The identification and characterisation of naturally occurring pro-resolution mediators including lipoxins and annexin A1 has prompted a shift in the field of anti-inflammation whereby resolution is now observed as an active process, triggered as part of a normal inflammatory response. This review will address the process of resolution, discuss available evidence for expression of pro-resolution factors in the reproductive tract and explore possible roles for resolution in physiological reproductive processes and associated pathologies. Reproduction (2011) 142 15-28

Glucocorticoids Sensitize Rat Placental Inflammatory Responses via Inhibiting Lipoxin A4 Biosynthesis1

“…ALOX15 exists in two isoforms: ALOX15 and ALOX15B [15]. ALOX15 oxygenates AA at both carbon 12 and 15, whereas ALOX15B converts AA exclusively to 15 (S)-HETE [24].…”

“…Lipoxins (LXs), bioactive products derived from arachidonic acid (AA) enzymatically by lipoxygenase (ALOX) and prostaglandinendoperoxide synthase (PTGS; also known as cyclooxygenase), function as ''stop signals'' in inflammation, which exert dual anti-inflammatory (inhibition of neutrophils and eosinophils infiltration) and proresolving (promotion of efferocytosis of apoptotic neutrophils) actions [14]. LXs also play vital roles in inflammation termination and homoeostasis restoration of reproductive system [15]. For instance, Lipoxin A 4 (LXA 4 ) inhibits LPS-stimulated proinflammatory IL6 and IL8 expression in human endometrium and deciduas [16,17].…”

The core transcriptome of mammalian placentas and the divergence of expression with placental shape

“…ANXA1 is involved in the resolution of the inammation response through inhibition of phospholipase A2 activity and signaling through the formyl peptide receptor family, and has previously been hypothesized to be important for the maintenance of the anti-inflammatory state during pregnancy [34]. ANXA2 is known to interact with S100A4, S100A6, S100A10, and S100A11 [35], and there is evidence for its interaction with S100P as well; it is involved in cell-cell interaction as well as vesicle trafficking and von Willibrand Factor secretion.…”

Influence of pathogenic bacteria species present in the postpartum bovine uterus on proteome profiles

“…The liberation of arachidonic acid, which is a rate-limiting step in the generation of prostaglandins, is mainly mediated by the hydrolytic action of PLA2 (Kudo et al 1993). As well as affecting the metabolism of arachidonic acid, ANXA1 inhibits the activity of other pro-inflammatory enzymes (nitric-oxide synthase in macrophages and cyclooxygenases in activated microglia) and has an inhibitory effect on both neutrophil and monocyte migration in inflammation (Parente and Solito 2004;Hutchinson et al 2011). Expression of ANXA1 is widespread, including high levels in macrophages and PMN (Perretti and D'Acquisto 2009) and human endometrial glandular epithelial and stromal cells (Li et al 2008).…”