Interleukin-6 and Type-I Collagen Production by Systemic Sclerosis Fibroblasts Are Differentially Regulated by Interleukin-17A in the Presence of Transforming Growth Factor-Beta 1

Frontiers in Immunology
Aleksandra Maria DufourCarlo Chizzolini

Abstract

Functional cytokine networks have been poorly characterized in systemic sclerosis (SSc). While interleukin-17A (IL-17A) is increased in SSc skin and other organs, its role is still debated, particularly considering fibrogenesis. We uncover here a dual function of IL-17A in the presence of transforming growth factor-β 1 (TGF-β), the master pro-fibrotic cytokine. In the one hand, we report an unexpected synergic activity resulting in enhanced production of IL-6 by dermal fibroblasts; in the other hand, a substantial inhibition of type I collagen (col-I) production. IL-17A or TGF-β enhanced the production of IL-6 by 8- to 16-folds when compared to control in healthy donors (HD) and SSc cultures. However, the joint presence of IL-17A and TGF-β resulted in robustly exuberant responses with levels of IL-6 up to 100-folds higher than those observed in untreated cells. Inhibition of NFκB signaling pathway preferentially inhibited the production of IL-6 driven by IL-17A in HD fibroblasts, while inhibition of PI3K preferentially inhibited the production of IL-6 driven by TGF-β. Interestingly, when p38 MAPK was inhibited, substantial reduction of IL-6 production was observed for both IL-17A and TGF-β. Consistently with the inhibition expe...Continue Reading

References

Nov 18, 2000·Arthritis and Rheumatism·K KurasawaI Iwamoto
Feb 14, 2002·The Journal of Investigative Dermatology·Franck Verrecchia, Alain Mauviel
Jan 18, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Serena FineschiCarlo Chizzolini
Oct 9, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Dolores M CortezBysani Chandrasekar
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Toshiyuki Yamamoto
Mar 11, 2008·Rheumatic Diseases Clinics of North America·John A Varga, Maria Trojanowska
Mar 18, 2008·European Journal of Cell Biology·Pierre-Jean Wipff, Boris Hinz
May 8, 2009·The New England Journal of Medicine·Armando GabrielliThomas Krieg
Oct 9, 2009·The Journal of Investigative Dermatology·Jennifer L SargentMichael L Whitfield
Feb 24, 2010·The Journal of Experimental Medicine·Mark S WilsonThomas A Wynn
Sep 25, 2010·Autoimmunity Reviews·Carlo ChizzoliniMarie-Elise Truchetet
Aug 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Su MiZhuo-Wei Hu
Nov 9, 2011·The American Journal of Pathology·Shun KitabaIchiro Katayama
Mar 10, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Taiji NakashimaHironobu Ihn
May 16, 2012·Annals of the Rheumatic Diseases·Korsa KhanVoon H Ong
Jul 10, 2012·Nature Medicine·Thomas A Wynn, Thirumalai R Ramalingam
Jan 31, 2013·European Cytokine Network·Nicolò Costantino Brembilla, Carlo Chizzolini
Jan 15, 2014·Immunity·Ceri A FieldingSimon A Jones
Jan 29, 2014·International Journal of Rheumatic Diseases·Anna Olewicz-GawlikPawel Hrycaj
Jul 26, 2014·Arthritis Research & Therapy·Lucille DesallaisYannick Allanore
Aug 20, 2014·Nature Reviews. Rheumatology·Robert Lafyatis
Apr 1, 2013·Clinical & Translational Immunology·Steven O'ReillyJacob M van Laar
Jun 23, 2015·The Journal of Clinical Investigation·Lisa M RiceRobert Lafyatis
Feb 4, 2016·Trends in Molecular Medicine·Audrey BeringerPierre Miossec
Jan 1, 2015·Nature Reviews. Disease Primers·Yannick AllanoreJohn Varga
May 19, 2017·Nature Immunology·Marc Veldhoen
Sep 19, 2017·Immunology Letters·Carlo ChizzoliniNicolò Costantino Brembilla
Jan 23, 2018·Matrix Biology : Journal of the International Society for Matrix Biology·Andrea Hermina GyörfiJörg H W Distler

❮ Previous
Next ❯

Citations

Nov 16, 2018·Clinical and Experimental Immunology·M Brown, S O'Reilly
Jun 4, 2019·Frontiers in Immunology·Nathaniel R West
May 21, 2020·American Journal of Physiology. Cell Physiology·Huocong Huang, Rolf A Brekken
May 11, 2019·Rheumatology International·Sakir AhmedVikas Agarwal
Sep 11, 2019·Experimental Dermatology·Xiangguang ShiWenyu Wu
May 6, 2020·Biomedicines·Blair Z JohnsonFiona M Wood
Jul 28, 2020·Journal of Autoimmunity·Julie C Worrell, Steven O'Reilly
Feb 13, 2021·Annual Review of Immunology·Saikat Majumder, Mandy J McGeachy
May 13, 2021·Immunity·Matthew B BuechlerShannon J Turley
Jul 16, 2021·Journal of Cosmetic Dermatology·Ya-Ping TsengChia-Hua Liang
Aug 20, 2021·Cytokine·Robert H JenkinsSimon A Jones

❮ Previous
Next ❯

Methods Mentioned

BETA
bronchoalveolar lavage
biopsy
ELISA
FCS

Clinical Trials Mentioned

NCT02453256

Software Mentioned

ImageJ
GraphPad Prism

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.