Objective
Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator that is involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM.
Materials and Methods
First-trimester CRP level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution LC-MS/MS. Circulating level of inflammatory cytokines IL-32, IL-6 and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines and related pathway proteins were assessed by RT-qPCR, western blot, immunohistochemistry or immunofluorescence.
Results
First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index, and was an independent correlation with the development of GDM. High-resolution LC-MS/MS revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased, and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α and p-p38 were up-regulated in the placental tissues with GDM. Neither IL-6 nor TNF-α was co-located with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM, and was related to placental-derived IL-32 expression, circulating IL-6 and TNF-α, glucose and insulin resistance index.
Conclusions
Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.