Skip to main content
Top
Published in: Inflammation Research 12/2012

01-12-2012 | Original Research Paper

Increased synovial expression of IL-27 by IL-17 in rheumatoid arthritis

Authors: Seung Hoon Baek, Seung Geun Lee, Young Eun Park, Geun Tae Kim, Chi Dae Kim, So Youn Park

Published in: Inflammation Research | Issue 12/2012

Login to get access

Abstract

Objectives and design

Interleukin (IL) 17 plays an important role in synovial inflammation and bone destruction in rheumatoid arthritis (RA), while IL-27 exerts a regulatory role in T cell-mediated immune responses. Our aim was to study the influence of IL-17 on IL-27 production in RA.

Materials and methods

Following injection of IL-17 in the knee joint of CIA mice, synovium was examined for IL-17 and IL-27 expression by western blot, real-time PCR, and immunohistochemistry. IL-17 and IL-27 levels were measured by ELISA in mouse bone marrow-derived dendritic cells (BM-DCs) and in synovial fluid (SF) macrophages from RA patients.

Results

IL-17 exacerbated disease progression in CIA mice. Histological analysis showed increased pannus formation associated with cartilage and bone erosion following injection with IL-17. The expression of IL-27 was increased in CIA mice. The expression of IL-17 and IL-27 was increased more in IL-17-injected CIA mice than in control mice. The majority of cells expressing IL-27 were co-localized with synovial macrophages. Increased expression of IL-27 by application of recombinant IL-17 was confirmed in CIA BM-DCs and in SF macrophages from RA patients.

Conclusion

IL-17 enhanced expression of IL-27 in synovial macrophages from RA patients and CIA mice, indicating an interaction between IL-17 and IL-27 as an autoregulatory mechanism.
Literature
1.
go back to reference Müller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2005;1:102–10.PubMedCrossRef Müller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2005;1:102–10.PubMedCrossRef
2.
go back to reference Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907–16.PubMedCrossRef Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907–16.PubMedCrossRef
4.
go back to reference Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, et al. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005;74:R784–95.CrossRef Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, et al. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005;74:R784–95.CrossRef
5.
go back to reference Hwang SY, Kim HY. Expression of IL-17 homologs and their receptors in the synovial cells of rheumatoid arthritis patients. Mol Cells. 2005;19:180–4.PubMed Hwang SY, Kim HY. Expression of IL-17 homologs and their receptors in the synovial cells of rheumatoid arthritis patients. Mol Cells. 2005;19:180–4.PubMed
6.
go back to reference Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171:6173–7.PubMed Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171:6173–7.PubMed
7.
go back to reference Toh ML, Gonzales G, Koenders MI, Tournadre A, Boyle D, Lubberts E, Zhou Y, Firestein GS, van den Berg WB, Miossec P. Role of interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression. PLoS One. 2010;5:e13416.PubMedCrossRef Toh ML, Gonzales G, Koenders MI, Tournadre A, Boyle D, Lubberts E, Zhou Y, Firestein GS, van den Berg WB, Miossec P. Role of interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression. PLoS One. 2010;5:e13416.PubMedCrossRef
8.
go back to reference Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, et al. IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol. 1998;160:3513–21.PubMed Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, et al. IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol. 1998;160:3513–21.PubMed
9.
go back to reference Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity. 2002;16:779–90.PubMedCrossRef Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity. 2002;16:779–90.PubMedCrossRef
10.
go back to reference Yoshida H, Yoshiyuki M. Regulation of immune responses by interleukin-27. Immunol Rev. 2008;226:234–47.PubMedCrossRef Yoshida H, Yoshiyuki M. Regulation of immune responses by interleukin-27. Immunol Rev. 2008;226:234–47.PubMedCrossRef
11.
go back to reference Hunter CA. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol. 2005;5:521–31.PubMedCrossRef Hunter CA. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol. 2005;5:521–31.PubMedCrossRef
12.
go back to reference Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan JF, Phillips JH, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol. 2004;172:2225–31.PubMed Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan JF, Phillips JH, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol. 2004;172:2225–31.PubMed
13.
go back to reference Villarino A, Hibbert L, Lieberman L, Wilson E, Mak T, Yoshida H, Kastelein RA, Saris C, Hunter CA. The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity. 2003;19:645–55.PubMedCrossRef Villarino A, Hibbert L, Lieberman L, Wilson E, Mak T, Yoshida H, Kastelein RA, Saris C, Hunter CA. The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity. 2003;19:645–55.PubMedCrossRef
14.
go back to reference Goldberg R, Wildbaum G, Zohar Y, Maor G, Karin N. Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27. J Immunol. 2004;173:1171–8.PubMed Goldberg R, Wildbaum G, Zohar Y, Maor G, Karin N. Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27. J Immunol. 2004;173:1171–8.PubMed
15.
go back to reference Pickens SR, Chamberlain ND, Volin MV, Mandelin AM 2nd, Agrawal H, Matsui M, Yoshimoto T, Shahrara S. Local expression of interleukin-27 ameliorates collagen-induced arthritis. Arthritis Rheum. 2011;63:2289–98.PubMedCrossRef Pickens SR, Chamberlain ND, Volin MV, Mandelin AM 2nd, Agrawal H, Matsui M, Yoshimoto T, Shahrara S. Local expression of interleukin-27 ameliorates collagen-induced arthritis. Arthritis Rheum. 2011;63:2289–98.PubMedCrossRef
16.
go back to reference Lee JH, Cho ML, Kim JI, Moon YM, Oh HJ, Kim GT, Ryu S, Baek SH, et al. Interleukin 17 (IL-17) increases the expression of Toll-like receptor-2, 4, and 9 by increasing IL-1beta and IL-6 production in autoimmune arthritis. J Rheumatol. 2009;36:684–92.PubMedCrossRef Lee JH, Cho ML, Kim JI, Moon YM, Oh HJ, Kim GT, Ryu S, Baek SH, et al. Interleukin 17 (IL-17) increases the expression of Toll-like receptor-2, 4, and 9 by increasing IL-1beta and IL-6 production in autoimmune arthritis. J Rheumatol. 2009;36:684–92.PubMedCrossRef
17.
go back to reference Fujimoto M, Serada S, Mihara M, Uchiyama Y, Yoshida H, Koike N, et al. Interleukin-6 blockade suppresses autoimmune arthritis inmice by the inhibition of inflammatory Th17 responses. Arthritis Rheum. 2008;58:3710–9.PubMedCrossRef Fujimoto M, Serada S, Mihara M, Uchiyama Y, Yoshida H, Koike N, et al. Interleukin-6 blockade suppresses autoimmune arthritis inmice by the inhibition of inflammatory Th17 responses. Arthritis Rheum. 2008;58:3710–9.PubMedCrossRef
18.
go back to reference Niedbala W, Cai B, Wei X, Patakas A, Leung BP, McInnes IB, Liew FY. Interleukin 27 attenuates collagen-induced arthritis. Ann Rheum Dis. 2008;67:1474–9.PubMedCrossRef Niedbala W, Cai B, Wei X, Patakas A, Leung BP, McInnes IB, Liew FY. Interleukin 27 attenuates collagen-induced arthritis. Ann Rheum Dis. 2008;67:1474–9.PubMedCrossRef
19.
go back to reference Cao Y, Doodes PD, Glant TT, Finnegan A. IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J Immunol. 2008;180:922–30.PubMed Cao Y, Doodes PD, Glant TT, Finnegan A. IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J Immunol. 2008;180:922–30.PubMed
20.
go back to reference Tanida S, Yoshitomi H, Ishikawa M, Kasahara T, Murata K, Shibuya H, et al. IL-27-producing CD14(+) cells infiltrate inflamed joints of rheumatoid arthritis and regulate inflammation and chemotactic migration. Cytokine. 2011;55:237–44.PubMedCrossRef Tanida S, Yoshitomi H, Ishikawa M, Kasahara T, Murata K, Shibuya H, et al. IL-27-producing CD14(+) cells infiltrate inflamed joints of rheumatoid arthritis and regulate inflammation and chemotactic migration. Cytokine. 2011;55:237–44.PubMedCrossRef
Metadata
Title
Increased synovial expression of IL-27 by IL-17 in rheumatoid arthritis
Authors
Seung Hoon Baek
Seung Geun Lee
Young Eun Park
Geun Tae Kim
Chi Dae Kim
So Youn Park
Publication date
01-12-2012
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 12/2012
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-012-0534-7

Other articles of this Issue 12/2012

Inflammation Research 12/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine