Systemic Inflammation Induced by microRNAs: Endometriosis-Derived Alterations in Circulating microRNA 125b-5p and Let-7b-5p Regulate Macrophage Cytokine Production

Nematian SE, Sepide Nematian, Sepide E Nematian, Ramanaiah Mamillapalli, Mamillapalli R, Trisha S Kadakia, Kadakia TS, Masoumeh Majidi Zolbin, Sarah Moustafa, Moustafa S, Hugh S. Taylor
The Journal of clinical endocrinology and metabolism · 2017 · vol. 103(1) , pp. 64–74 · doi:10.1210/jc.2017-01199 · PMID:29040578 · W2762825621
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Endometriosis-associated circulating miRNAs 125b-5p and Let-7b-5p were found to regulate macrophage cytokine production, contributing to inflammation in this condition.

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Abstract

CONTEXT: Endometriosis is characterized by aberrant inflammation. We previously reported increased levels of microRNA (miRNA) 125b-5p and decreased levels of miRNA Let-7b-5p in serum of patients with endometriosis. OBJECTIVE: Determine the regulatory function of miRNAs 125b-5p and Let-7b-5p on production of proinflammatory cytokines in endometriosis. DESIGN: Case-control study. SETTING: University hospital. PATIENTS: Women with (20) and without (26) endometriosis; human U937 macrophage cell line. INTERVENTION: Sera were collected from surgically diagnosed patients and differentiated U937 cells that were transfected with miRNAs 125b-5p and Let-7b-5p mimics and inhibitor. MAIN OUTCOME MEASURES: Enzyme-linked immunosorbent assay for tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β levels and quantitative real-time polymerase chain reaction for expression of miRNAs 125b-5p and Let-7b-5p in sera of patients with and without endometriosis. Transfected macrophages were evaluated for expression of inflammatory cytokines, intracellular production, and secretion of these cytokines. RESULTS: We noted substantial elevation of TNF-α, IL-1β, and IL-6, marked upregulation of miRNA 125b, and considerable downregulation of Let-7b in sera of patients with endometriosis vs control. There was a positive correlation between miRNA 125b levels and TNF-α, IL-1β, and IL-6 and a negative correlation between miRNA Let-7b levels and TNF-α in sera of patients with endometriosis. Transfection experiments showed a noteworthy upregulation of TNF-α, IL-1β, IL-6, and IL-8 in macrophages transfected with miRNA 125b mimic or Let-7b inhibitor. The secreted cytokine protein levels and intracellular imaging studies closely correlate with the messenger RNA changes. CONCLUSIONS: Endometriosis-derived miRNAs regulate macrophage cytokine production that contributes to inflammation associated with this condition.

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Condition tags

endometriosis

MeSH descriptors

Cytokines Endometriosis Inflammation Macrophages MicroRNAs Adult Adult Case-Control Studies Case-Control Studies Cell Differentiation Cell Differentiation Cytokines Cytokines Endometriosis Endometriosis Female Female Humans Humans Inflammation

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