Behavior of tumor necrosis factor-α and tumor necrosis factor receptor 1/tumor necrosis factor receptor 2 system in mononuclear cells recovered from peritoneal fluid of women with endometriosis at different stages

During endometriosis, a breakdown occurs in endometrial and peritoneal homeostasis caused by cytokine-induced cell proliferation and dysregulation of apoptosis. We studied tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1, and TNFR2 gene expression at both messenger RNA (mRNA) and protein levels in peritoneal fluid (PF) mononuclear cells (PFMCs), the percentages of these cells bearing the same markers, and soluble TNF-α (sTNF-α) values in PF of 80 women with endometriosis. We found that TNFR1 mRNA and protein levels, the percentages of TNFR1-bearing PFMCs, and sTNF-α values decreased from minimal to severe stages of the disease. Instead, TNF-a and TNFR2 mRNA and protein levels, the percentages of membrane TNF-α (mTNF-α)- and TNFR2-bearing PFMCs increased as the disease worsened. These data allow us to hypothesize that, in early stages, the high percentages of TNFR1-bearing PFMCs and the high levels of sTNF-α could address signal toward complex I pathway, favoring the inflammatory response. With the worsening of the disease, the low percentages of TNFR1-bearing PFMCs are probably due to decreased TNFR1 mRNA transcription and protein translation rate. In early stages (minimal and mild), the percentages of both TNFR2- and mTNF-α-bearing PFMCs are so low, due to decreased mRNA transcription and protein translation rate, that subsequent cellular events may depend minimally by this interaction. The high levels of sTNF-α may be rerouted to bind TNFR1. In contrast, in the moderate and severe stages, the high percentages of TNFR2-bearing PFMCs may be saturated by high percentages of mTNF-α-bearing PFMCs, triggering death process. So, in endometriosis, each component of the TNF-α/TNFRs system may trigger opposite cellular fate. Similar content being viewed by others

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