A clear and present danger: inflammasomes DAMPing down disorders of pregnancy

Khan, Raheela; Hay, Daniel

doi:10.1093/humupd/dmu059

Cited by 48 publications

(41 citation statements)

References 235 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Placental trophoblasts, endothelial cells and macrophages can sense and respond to a variety of infectious agents by the presence of the pattern recognition receptors (PRRs). The PRRs have the ability to sense pathogen-associated molecular patterns (PAMPs) that are expressed by microbes, as well as noninfectious (sterile inflammation) host-derived damage associated molecular patterns (DAMPs) including reactive oxygen species, uric acid, cholesterol, microparticles, and exosomes (namely alarmins) [40,41] ( Figure 2). When activated, the inflammasome machinery has the potential to promote maturation and release of pro-inflammatory cytokines including the release of danger signals, as well as pyroptosis, a rapid, pro-inflammatory form of cell death [42].…”

Section: Inflammasomesmentioning

confidence: 99%

Inflammasomes—A Molecular Link for Altered Immunoregulation and Inflammation Mediated Vascular Dysfunction in Preeclampsia

Murthi

Pinar

Dimitriadis

et al. 2020

IJMS

View full text Add to dashboard Cite

Preeclampsia (PE) is a pregnancy-specific multisystem disorder and is associated with maladaptation of the maternal cardiovascular system and abnormal placentation. One of the important characteristics in the pathophysiology of PE is a dysfunction of the placenta. Placental insufficiency is associated with poor trophoblast uterine invasion and impaired transformation of the uterine spiral arterioles to high capacity and low impedance vessels and/or abnormalities in the development of chorionic villi. Significant progress in identifying potential molecular targets in the pathophysiology of PE is underway. The human placenta is immunologically functional with the trophoblast able to generate specific and diverse innate immune-like responses through their expression of multimeric self-assembling protein complexes, termed inflammasomes. However, the type of response is highly dependent upon the stimuli, the receptor(s) expressed and activated, the downstream signaling pathways involved, and the timing of gestation. Recent findings highlight that inflammasomes can act as a molecular link for several components at the syncytiotrophoblast surface and also in maternal blood thereby directly influencing each other. Thus, the inflammasome molecular platform can promote adverse inflammatory effects when chronically activated. This review highlights current knowledge in placental inflammasome expression and activity in PE-affected pregnancies, and consequently, vascular dysfunction in PE that must be addressed as an interdependent interactive process.

show abstract

Section: Inflammasomesmentioning

confidence: 99%

Inflammasomes—A Molecular Link for Altered Immunoregulation and Inflammation Mediated Vascular Dysfunction in Preeclampsia

Murthi

Pinar

Dimitriadis

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…In the present study, the expression level of IL-1β in the fallopian tubes was found to be higher in the stimulated groups than in the unstimulated control group. Several studies have indicated that higher levels of IL-1β negatively affect the fertilization process (14-16), embryonic implantation, and pregnancy outcomes (18)(19)(20), and can cause several different complications during pregnancy (21) and can be employed as a marker for tubal pregnancy (22). The elevated inflammatory response observed within the fallopian tube due to higher IL-1β levels, accompanied by the disturbed histoarchitecture of the fallopian tube, might directly affect the fertilization process.…”

Section: Discussionmentioning

confidence: 99%

Ovarian stimulation induces high expression of interleukin-1β and disrupts the histological features of the fallopian tube

Moussa¹,

Farouk²

2019

Turk J Vet Anim Sci

View full text Add to dashboard Cite

The objective of this study was to investigate whether there is an association between ovarian stimulation and interrupted gamete interaction in the rat fallopian tube in vivo. We evaluated the protein expression of interleukin-1β (IL-1β) via immunohistochemistry and assessed the key histological features of the ovaries, fallopian tubes, and uteri of the rats following treatment with mild (15 IU) and high (30 IU) doses of gonadotropins compared to an unstimulated control group. The serum concentration of estradiol was also determined by immunoassay. The results revealed that high levels of circulating estrogen were associated with higher expression of the IL-1β protein in the ovaries and fallopian tubes of highly stimulated rats than in those of the mildly stimulated and unstimulated control groups. In contrast, endometrial IL-1β immunoexpression was not affected by ovarian stimulation. The histological features of the fallopian tubes were also dramatically altered upon ovarian stimulation, reducing the efficiency of the fallopian tube. In conclusion, the resulting high circulating estrogen level disrupts the histological features of the fallopian tubes and can lead to higher expression of IL-1β, thus negatively affecting gamete interactions in vivo. These results provide useful information regarding the lower fertilization rate observed following ovarian stimulation.

show abstract

“…Interestingly, cell-free DNA levels have been found increased in PE compared to healthy pregnant volunteers. 24 These mediators are non-microbial "damage" or "danger" molecules also known as alarmins that are found at sites not normally associated with their function due to cell stress or damage and can cause sterile inflammation, in part, by the recruitment and assembly of inflammasomes. 24 These mediators are non-microbial "damage" or "danger" molecules also known as alarmins that are found at sites not normally associated with their function due to cell stress or damage and can cause sterile inflammation, in part, by the recruitment and assembly of inflammasomes.…”

Section: Trophob L a S T Inva S Ion During Preg Nan C Ymentioning

confidence: 99%

“…37,38 One of the most important host defence mechanisms against different intrusive microorganisms is the inflammatory response initiated by DAMPs. 24 These mediators are non-microbial "damage" or "danger" molecules also known as alarmins that are found at sites not normally associated with their function due to cell stress or damage and can cause sterile inflammation, in part, by the recruitment and assembly of inflammasomes. 39 The first described DAMPs include eATP, 40 HMGB1, 41 as well as crystalline mediators, for example, MSU.…”

Section: Trophob L a S T Inva S Ion During Preg Nan C Ymentioning

confidence: 99%

Inflammation—The role of ATP in pre‐eclampsia

2019

View full text Add to dashboard Cite

Sterile inflammation may be initiated by molecules in the host organism that signal “damage” or “danger” also known as danger‐associated molecular pattern (DAMPs). In pre‐eclampsia (PE), a variety of DAMPs may be involved in the etiology or exacerbation of the disorder. Adenosine 5’‐triphosphate (ATP) is a key intracellular energy molecule as well as a ligand for purinergic receptors. In humans, under physiological conditions, extracellular ATP (eATP) levels are distinctly low, but can rise to several hundred fold when cells become injured, stressed, or even necrotic. This often initiates a sterile inflammatory response with eATP acting as a DAMP. Extracellular ATP and its derivative nucleotides synthetized by endonucleotidases exhibit many of their effects through purinergic receptors, via inflammatory cascades and the production of proinflammatory molecules. This is clearly seen in the P2X7 gated receptor, which is linked to release of cytokines of the interleukin‐1 family. Considering its fundamental role in innate immunity, an imbalance of P2X7 receptor activation may lead to deleterious effects in the coordination of placental vessel tone via the synthesis of various proinflammatory cytokines. This review explores the implication of DAMPs, specifically ATP and uric acid in the inflammation associated with PE.

show abstract

A clear and present danger: inflammasomes DAMPing down disorders of pregnancy

Cited by 48 publications

References 235 publications

Inflammasomes—A Molecular Link for Altered Immunoregulation and Inflammation Mediated Vascular Dysfunction in Preeclampsia

Inflammasomes—A Molecular Link for Altered Immunoregulation and Inflammation Mediated Vascular Dysfunction in Preeclampsia

Ovarian stimulation induces high expression of interleukin-1β and disrupts the histological features of the fallopian tube

Inflammation—The role of ATP in pre‐eclampsia

Contact Info

Product

Resources

About