Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
April 2012 Volume 29 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April 2012 Volume 29 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

IL-33 regulates TNF-α dependent effects in synovial fibroblasts

  • Authors:
    • Elke Kunisch
    • Saritha Chakilam
    • Muktheshwar Gandesiri
    • Raimund W. Kinne
  • View Affiliations / Copyright

    Affiliations: Experimental Rheumatology Unit, Department of Orthopedics, University Hospital Jena, Kloster­lausnitzer Str. 81, D-07607 Eisenberg, Germany
    Copyright: © Kunisch et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 530-540
    |
    Published online on: January 10, 2012
       https://doi.org/10.3892/ijmm.2012.883
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The recently described IL-33 acts as a pro-inflammatory cytokine, inducing the expression of multiple responses in the target cells. Although a nuclear localization of IL-33 has been described, its exact functional relevance is presently unknown. The present study was conducted to analyze the effects of IL-33 on the TNF-α induced synthesis of the pro-inflammatory mediators IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) and the pro-destructive molecules matrix metalloproteinase-1 (MMP-1), MMP-3, and TIMP-1 of rheumatoid arthritis synovial fibroblast (RA-SFs) using RNA overexpression and silencing. TNF-α significantly induced IL-33 mRNA expression and protein synthesis in RA-SFs. TNF-α-induced IL-33 protein expression was mediated via p38 signaling. Immunohistochemistry for IL-33 clearly showed that nuclear translocation of IL-33 was induced in TNF-α stimulated RA-SFs. IL-33 overexpression enhanced TNF-α-induced pro-inflammatory and pro-destructive functions in RA-SFs. IL-33 silencing significantly downregulated TNF-α-induced pro-inflammatory functions, whereas TNF-α-induced pro-destructive functions were less influenced by IL-33 silencing. This study identifies IL-33 as a critical regulator/enhancer of TNF-α-induced functions in RA-SFs, pointing to a central role of this cytokine in the perpetuation of pro-inflammatory and pro-destructive processes in rheumatoid arthritis (RA) and other inflammatory and degenerative diseases.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

View References

1 

J SchmitzA OwyangE OldhamIL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokinesImmunity23479490200510.1016/j.immuni.2005.09.01516286016

2 

ES BaekkevoldM RoussigneT YamanakaMolecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venulesAm J Pathol1636979200310.1016/S0002-9440(10)63631-012819012

3 

V CarriereL RousselN OrtegaIL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivoProc Natl Acad Sci USA104282287200710.1073/pnas.060685410417185418

4 

CA HudsonGP ChristophiRC GruberJR WilmoreDA LawrencePT MassaInduction of IL-33 expression and activity in central nervous system gliaJ Leukoc Biol84631643200810.1189/jlb.120783018552204

5 

AM KuchlerJ PollheimerJ BaloghNuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activationAm J Pathol17312291242200810.2353/ajpath.2008.08001418787100

6 

M IikuraH SutoN KajiwaraIL-33 can promote survival, adhesion and cytokine production in human mast cellsLab Invest87971978200710.1038/labinvest.370066317700564

7 

D MoulinO DonzeD Talabot-AyerF MezinG PalmerC GabayInterleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cellsCytokine40216225200710.1016/j.cyto.2007.09.01318023358

8 

R KakkarRT LeeThe IL-33/ST2 pathway: therapeutic target and novel biomarkerNat Rev Drug Discov7827840200810.1038/nrd266018827826

9 

C CayrolJP GirardThe IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1Proc Natl Acad Sci USA10690219026200910.1073/pnas.081269010619439663

10 

C MoussionN OrtegaJP GirardThe IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’?PLoS One3e3331200818836528

11 

BP LeungD XuS CulshawIB McInnesFY LiewA novel therapy of murine collagen-induced arthritis with soluble T1/ST2J Immunol173145150200410.4049/jimmunol.173.1.14515210768

12 

D XuHR JiangP KewinIL-33 exacerbates antigen-induced arthritis by activating mast cellsProc Natl Acad Sci USA1051091310918200810.1073/pnas.080189810518667700

13 

G PalmerD Talabot-AyerC LamacchiaInhibition of interleukin-33 signaling attenuates the severity of experimental arthritisArthritis Rheum60738749200910.1002/art.2430519248109

14 

WA Verri JrFO SoutoSM VieiraIL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapyAnn Rheum Dis6916971703201010.1136/ard.2009.12265520472598

15 

Y MatsuyamaH OkazakiH TamemotoIncreased levels of interleukin 33 in sera and synovial fluid from patients with active rheumatoid arthritisJ Rheumatol371825201010.3899/jrheum.09049219918048

16 

S KaiedaK ShinPA NigrovicSynovial fibroblasts promote the expression and granule accumulation of tryptase via interleukin-33 and its receptor ST-2 (IL1RL1)J Biol Chem2852147821486201010.1074/jbc.M110.11499120427273

17 

G PalmerS TrollietD Talabot-AyerF MezinD MagneC GabayPre-interleukin-1alpha expression reduces cell growth and increases interleukin-6 production in SaOS-2 osteosarcoma cells: differential inhibitory effect of interleukin-1 receptor antagonist (icIL-1Ra1)Cytokine31153160200510.1016/j.cyto.2005.03.007

18 

S SharmaN KulkMF NoldThe IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokinesJ Immunol18054775482200810.4049/jimmunol.180.8.547718390730

19 

FC ArnettSM EdworthyDA BlochThe American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritisArthritis Rheum31315324198810.1002/art.17803103023358796

20 

T ZimmermannE KunischR PfeifferIsolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture - primary culture cells markedly differ from fourth-passage cellsArthritis Res37276200110.1186/ar142

21 

A HirthA SkapenkoRW KinneF EmmrichH Schulze-KoopsU SackCytokine mRNA and protein expression in primary-culture and repeated-passage synovial fibroblasts from patients with rheumatoid arthritisArthritis Res4117125200210.1186/ar39111879547

22 

N SwaroopF ChenL WangS DokkaD ToledoY RojanasakulInhibition of nuclear transcription factor-kappaB by specific IkappaB kinase peptide inhibitorPharm Res1816311633200110.1023/A:101305101909811758774

23 

DB GlassHC ChengL Mende-MuellerJ ReedDA WalshPrimary structural determinants essential for potent inhibition of cAMP-dependent protein kinase by inhibitory peptides corresponding to the active portion of the heat-stable inhibitor proteinJ Biol Chem264880288101989

24 

S AlsalamehRJ AminE KunischHE JasinRW KinnePreferential induction of prodestructive matrix metalloproteinase-1 and proinflammatory interleukin 6 and prostaglandin E2 in rheumatoid arthritis synovial fibroblasts via tumor necrosis factor receptor-55J Rheumatol30168016902003

25 

E KunischM GandesiriR FuhrmannA RothR WinterRW KinnePredominant activation of MAP kinases and pro-destructive/pro-inflammatory features by TNF alpha in early-passage synovial fibroblasts via TNF receptor-1: failure of p38 inhibition to suppress matrix metalloproteinase-1 in rheumatoid arthritisAnn Rheum Dis6610431051200710.1136/ard.2006.062521

26 

D PohlersA BeyerD KoczanT WilhelmHJ ThiesenRW KinneConstitutive upregulation of the transforming growth factor-beta pathway in rheumatoid arthritis synovial fibroblastsArthritis Res Ther9R59200710.1186/ar221717594488

27 

D PretzelD PohlersS WeinertRW KinneIn vitro model for the analysis of synovial fibroblast-mediated degradation of intact cartilageArthritis Res Ther11R25200910.1186/ar261819226472

28 

LM CarruthS DemczukSB MizelInvolvement of a calpain-like protease in the processing of the murine interleukin 1 alpha precursorJ Biol Chem266121621216719912061304

29 

WM SidersJC KlimovitzSB MizelCharacterization of the structural requirements and cell type specificity of IL-1 alpha and IL-1 beta secretionJ Biol Chem268221702217419938408078

30 

FM BrennanIB McInnesEvidence that cytokines play a role in rheumatoid arthritisJ Clin Invest11835373545200810.1172/JCI3638918982160

31 

B GrimbacherWK AicherHH PeterH EibelTNF-alpha induces the transcription factor Egr-1, pro-inflammatory cytokines and cell proliferation in human skin fibroblasts and synovial lining cellsRheumatol Int17185192199810.1007/s0029600500329542779

32 

H KitasatoM NodaT AkahoshiActivated Ras modifies the proliferative response of rheumatoid synovial cells to TNF-alpha and TGF-alphaInflamm Res50592597200110.1007/PL0000023911822784

33 

K AupperleB BennettZ HanD BoyleA ManningG FiresteinNF-kappa B regulation by I kappa B kinase-2 in rheumatoid arthritis synoviocytesJ Immunol16627052711200110.4049/jimmunol.166.4.270511160335

34 

Y TakadaH IchikawaA PataerS SwisherBB AggarwalGenetic deletion of PKR abrogates TNF-induced activation of IkappaBalpha kinase, JNK, Akt and cell proliferation but potentiates p44/p42 MAPK and p38 MAPK activationOncogene2612011212200710.1038/sj.onc.120990616924232

35 

L RousselM ErardC CayrolJP GirardMolecular mimicry between IL-33 and KSHV for attachment to chromatin through the H2A-H2B acidic pocketEMBO Rep910061012200810.1038/embor.2008.14518688256

36 

M Funakoshi-TagoK TagoM HayakawaTRAF6 is a critical signal transducer in IL-33 signaling pathwayCell Signal2016791686200810.1016/j.cellsig.2008.05.01318603409

37 

T Pecaric-PetkovicSA DidichenkoS KaempferN SpieglCA DahindenHuman basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33Blood11315261534200910.1182/blood-2008-05-15781818955562

38 

M SuzukawaM IikuraR KoketsuAn IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptorJ Immunol18159815989200810.4049/jimmunol.181.9.598118941187

39 

P BuflerF Gamboni-RobertsonT AzamSH KimCA DinarelloInterleukin-1 homologues IL-1F7b and IL-18 contain functional mRNA instability elements within the coding region responsive to lipopolysaccharideBiochem J381503510200410.1042/BJ2004021715046617

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kunisch E, Chakilam S, Gandesiri M and Kinne RW: IL-33 regulates TNF-α dependent effects in synovial fibroblasts . Int J Mol Med 29: 530-540, 2012.
APA
Kunisch, E., Chakilam, S., Gandesiri, M., & Kinne, R.W. (2012). IL-33 regulates TNF-α dependent effects in synovial fibroblasts . International Journal of Molecular Medicine, 29, 530-540. https://doi.org/10.3892/ijmm.2012.883
MLA
Kunisch, E., Chakilam, S., Gandesiri, M., Kinne, R. W."IL-33 regulates TNF-α dependent effects in synovial fibroblasts ". International Journal of Molecular Medicine 29.4 (2012): 530-540.
Chicago
Kunisch, E., Chakilam, S., Gandesiri, M., Kinne, R. W."IL-33 regulates TNF-α dependent effects in synovial fibroblasts ". International Journal of Molecular Medicine 29, no. 4 (2012): 530-540. https://doi.org/10.3892/ijmm.2012.883
Copy and paste a formatted citation
x
Spandidos Publications style
Kunisch E, Chakilam S, Gandesiri M and Kinne RW: IL-33 regulates TNF-α dependent effects in synovial fibroblasts . Int J Mol Med 29: 530-540, 2012.
APA
Kunisch, E., Chakilam, S., Gandesiri, M., & Kinne, R.W. (2012). IL-33 regulates TNF-α dependent effects in synovial fibroblasts . International Journal of Molecular Medicine, 29, 530-540. https://doi.org/10.3892/ijmm.2012.883
MLA
Kunisch, E., Chakilam, S., Gandesiri, M., Kinne, R. W."IL-33 regulates TNF-α dependent effects in synovial fibroblasts ". International Journal of Molecular Medicine 29.4 (2012): 530-540.
Chicago
Kunisch, E., Chakilam, S., Gandesiri, M., Kinne, R. W."IL-33 regulates TNF-α dependent effects in synovial fibroblasts ". International Journal of Molecular Medicine 29, no. 4 (2012): 530-540. https://doi.org/10.3892/ijmm.2012.883
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team