Advanced glycation endproducts mediate pro-inflammatory actions in human gestational tissues via nuclear factor-κB and extracellular signal-regulated kinase 1/2

Abstract

Processes of human labour include increased oxidative stress, formation of inflammatory mediators (e.g. cytokines) and uterotonic phospholipid metabolites (e.g. prostaglandins). In non-gestational tissues, advanced glycation endproducts (AGE) induce the expression of pro-inflammatory molecules through mitogen-activated protein kinase and nuclear factor kB (NF-kB)-dependent pathways. Thus, the aim of this study was to investigate the effects of AGE on 8-isoprostane (a marker of oxidative stress), pro-inflammatory cytokine and prostaglandin release in human gestational tissues, and to define the signalling pathways involved. Human placenta and gestational membranes (amnion and choriodecidua combined; nZ5) were incubated in the absence or presence of AGE-BSA (0 . 25, 0 . 5, 1 and 2 mg/ml) for 18 h. AGE significantly increased in vitro release of tumour necrosis factor-a, interleukin (IL)-1b, IL-6, IL-8, prostaglandin (PG)E 2 , PGF 2a and 8-isoprostane from human placenta and gestational membranes. This was associated with a concomitant increase in NF-kB p65 activation and ERK 1/2 phosphorylation. AGE-stimulated 8-isoprostane, cytokine and prostaglandin production was significantly suppressed by the ERK 1/2 inhibitor U0126 and the NF-kB inhibitor BAY 11-7082. In conclusion, AGE mediates inflammatory actions in human gestational tissues. Protein kinases and the NF-kB pathway play an essential role in AGE signalling in human gestational tissues.

Immunolocalization of advanced glycation end products in human diabetic eyes: an immunohistochemical study

“…It is known that hyperglycemia promotes inflammation through the induction of cytokine secretion by several cell types including monocytes. AGE induces the expression of pro-inflammatory molecules through mitogen-activated protein kinase and nu-clear factor kappaB-dependent pathways [23]. Furthermore, AGE is believed to play an important role in the onset of uveitis in Vogt-Koyanagi-Harada disease [24].…”

Short Communication The functional polymorphisms -429T>C and -374T>A of the RAGE gene promoter are not associated with gestational diabetes in Euro-Brazilians

“…RAGE is expressed in several tissues including human myometrium, chorionic villi and placenta (Lappas et al, 2007) and is involved in diabetes complications such as tissue injury, sustained inflammation and vascular complications (Bierhaus et al, 2005;Bierhaus and Nawroth, 2009). AGEs are the best studied ligands of RAGE that also bind β-amyloid peptide, S100/calgranulins and amphoterin (Bierhaus et al, 2005).…”

“…It has been shown that AGEs have pro-inflammatory actions in human gestational tissues, increasing oxidative stress, release of cytokines and prostaglandins (Lappas et al, 2007;Pertynska-Marczewska et al, 2009), suggesting an involvement of the AGE-RAGE interaction in gestational diabetes pathogenesis.…”

Stres oksydacyjny indukowany hiperglikemią w cukrzycy ciążowej (GDM)

“…prostaglandins) as well as in adverse pregnancy outcomes. In support of this, AGEs significantly increases in vitro release of tumour necrosis factor-a (TNF-a), interleukin IL-1b, IL-6, IL-8, prostaglandin (PG)E2, PGF2a and 8-isoprostane from human placenta and gestational membranes with a concomitant increase in NF-kB p65 activation and ERK 1/2 phosphorylation [34], and concentrations of AGE-modified products in umbilical cord blood increase with gestation progression and Figure 2. Contribution of the polyol pathway to increased oxidative stress during hyperglycaemia.…”