Hyperglycemia induces inflammatory mediators in the human chorionic villous

Abstract

This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous. Maternal plasma and placental levels of inflammatory factors (IL-1β, IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous stroma cells showed strong immunoreactivity to CD68. In addition, with syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS, MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic groups suggesting the inflammasome may be assembled in these pregnant women. The NFKB activity also exhibited higher levels in hyperglycemic groups, which might imply in pro-inflammatory cytokines production. In summary, increased maternal glucose levels during pregnancy changed systemic and placental inflammatory patterns, which occurred in parallel with the expression of inflammasome factors and processing and secretion of the pro-inflammatory cytokine IL-1β. These results suggest an inflammatory condition in all gestational hyperglycemic conditions, even in hyperglycemia that is less severe than gestational or overt diabetes, likely associated with inflammasome activation and inflammatory cytokine secretion. Inflammasome activation as a possible source of inflammatory factors may be an important target to be considered while managing hyperglycemia and preventing adverse pregnancy outcomes.

The effect of NLRP inflammasome on the regulation of AGEs‐induced inflammatory response in human periodontal ligament cells

“…32 Hence, besides NLRP3, NLRP1 inflammasome may be assembled under hyperglycemia. 33 Chang P's study. 5 We speculated that besides NF-κB signal pathway, Besides NLRs, NF-κB pathway activation has been acknowledged to be important in diabetes for altering cytokine secretion and antigen presentation in innate immune cells.…”

“…In addition, as the first NLR shown to form inflammasome, NLRP1 functions to activate caspase‐1 and subsequently cleaves IL‐1β and IL‐18 . Hence, besides NLRP3, NLRP1 inflammasome may be assembled under hyperglycemia . A study conducted by Meng X, et al., revealed that high glucose induced neuroinflammation through activation of NLRP1‐inflammasome, suggesting that under hyperglycemia, NLRP1‐inflammasome may contribute to inflammatory response.…”

Role of the NLRP3 Inflammasome in Preeclampsia

“…GDM is also classed as an obesity-related pregnancy complication. In GDM, high levels of serum glucose are associated with increased inflammation in blood as well as placenta (165). Excess glucose induces IL-1β secretion from human trophoblast cells depending on the NLRP3 inflammasome (166).…”

Ginsenoside Rg1 Alleviates Podocyte Injury Induced by Hyperlipidemia via Targeting the mTOR/NF-κB/NLRP3 Axis

“…While IL-1 β mediates podocyte injury and renal inflammation [ 54 ], NLRP3 is involved in the pathogenesis of chronic kidney disease [ 55 , 56 ]. Since hyperlipidemia can activate multiple inflammasomes [ 57 ], we knocked down NLRP3 in podocytes and found that absence of NLRP3 inhibited pyroptosis, indicating that it initiates pyroptosis in podocytes during DN.…”