Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells

Journal article

Multisystem inflammatory syndrome in children (MIS-C) is an imperative pediatric inflammatory condition closely linked to COVID-19, which garners substantial attention since the onset of the pandemic. Like Kawasaki illness, this condition is characterized by an overactive immune response, leading to symptoms including pyrexia, cardiac and renal complications. To elucidate the pathogenesis of MIS-C and identify potential biomarkers, we conducted an extensive examination of specific cytokines (IL-6, IL-1β, IL-6R, IL-10, and TNF-α) and microRNA (miRNA) expression profiles at various intervals (ranging from 3 to 20 days) in the peripheral blood sample of a severely affected MIS-C patient. Our investigation revealed a gradual decline in circulating levels of IL-6, IL-1β, IL-10, and TNF-α following intravenous immune globulin (IVIG) therapy. Notably, IL-6 exhibited a significant reduction from 74.30 to 1.49 pg./mL, while IL-6R levels remained consistently stable throughout the disease course. Furthermore, we observed an inverse correlation between the expression of hsa-miR-596 and hsa-miR-224-5p and the aforementioned cytokines. Our findings underscore a robust association between blood cytokine and miRNA concentrations and the severity of MIS-C. These insights enhance our understanding of the genetic regulatory mechanisms implicated in MIS-C pathogenesis, offering potential avenues for early biomarker detection and therapy monitoring through miRNA analysis

Authors: Zegeye, MM; Lindkvist, M; Fälker, K; Kumawat, AK; Paramel, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Cell Communication and Signaling
• Volume: 16
• Issue: 1
• Pages: 55-55
• Publication date: 2018-09-05
• DOI: 10.1186/s12964-018-0268-4
• EISSN: 1478-811X
• ISSN: 1478-811X
• Language: English
• Keywords: Protein kinase B; PI3K/AKT/mTOR pathway; Notch signaling pathway; MAPK/ERK pathway; Chemokine; Immunology; Hes3 signaling axis; Glycoprotein 130; Inflammation; Biology; Signal transduction; Cancer research; STAT3; Cell biology