Interleukin (IL)-6 Inhibits IL-27- and IL-30-Mediated Inflammatory Responses in Human Monocytes.

Frontiers in Immunology
Carlene PetesKatrina Gee

Abstract

Interleukin (IL)-30, the IL-27p28 subunit of the heterodimeric cytokine IL-27, acts as an antagonist of IL-27 and IL-6 signaling in murine cells via glycoprotein 130 (gp130) receptor and additional binding partners. Thus far, functions of IL-30 have not been fully elucidated in human cells. We demonstrate that like IL-27, IL-30 upregulated TLR4 expression to enhance lipopolysaccharide-induced TNF-α production in human monocytes; however, these IL-30-mediated activities did not reach the same levels of cytokine induction compared to IL-27. Interestingly, IL-30- and IL-27-mediated interferon-γ-induced protein 10 (IP-10) production required WSX-1 engagement and signal transducer and activator of transcription (STAT) 3 phosphorylation; furthermore, IL-30 induced STAT phosphorylation after 16 h, whereas IL-27 induced STAT phosphorylation within 30 min. This prompted us to examine if a secondary mediator was required for IL-30-induced pro-inflammatory functions, and hence we examined IL-6-related molecules. Combined with inhibition of soluble IL-6 receptor α (sIL-6Rα) and data showing that IL-6 inhibited IL-30/IL-27-induced IP-10 expression, we demonstrate a role for sIL-6Rα and gp130 in IL-30-mediated activity in human cells.

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Citations

Sep 23, 2018·The Journal of Biological Chemistry·Carlene PetesKatrina Gee
Nov 15, 2018·Modern Rheumatology·Atsushi OgataKazuyuki Yoshizaki
Apr 23, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Olena KourkoKatrina Gee
Nov 26, 2019·Journal of Cardiovascular Pharmacology·Anthony T BejjaniFouad A Zouein
May 16, 2019·Expert Opinion on Drug Delivery·Atsushi OgataKeiji Maeda
Sep 25, 2019·International Journal of Molecular Sciences·Luis E Soria-JassoEduardo Fernández-Martínez
Nov 30, 2018·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ali Berkant AvciGerd Rüdiger Burmester
Nov 5, 2019·Frontiers in Oncology·Olena KourkoKatrina Gee
Feb 6, 2020·Frontiers in Immunology·Sofia Noli TruantMarisa M Fernández
Aug 31, 2020·Current Medical Science·Zai-Yu ZhangYu-Mei Ding
Nov 5, 2020·International Reviews of Immunology·Zahra BeizaviAbbas Ghaderi
Mar 18, 2021·Clinical & Translational Immunology·Marie-Laure ClénetNathalie Arbour
Apr 27, 2021·The Journal of International Medical Research·Nergez Sabah OmarXuebiao Peng

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Methods Mentioned

BETA
transfection
ELISA
FACS
protein assay
flow cytometry
protein folding
as surface plasmon

Software Mentioned

FlowJo
expresso
COFFEE
Stattic

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