Skip to main content

Advertisement

SpringerLink
Log in

Role of nuclear factor κb in synovial inflammation

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

The evaluation of molecular pathways has revealed novel insights into the pathophysiology of rheumatoid arthritis in the last several years. Gene transcription factors such as nuclear factor κB (NFκB) are activated by extracellular signals or cell-to-cell interactions that are converted into intracellular activation signals through receptor molecules located in the cell membrane. The number of known genes being translated after NFκB activation is increasing steadily. These genes includes cytokines, chemokines, growth factors, cellular ligands, and adhesion molecules. Because many of these genes are part of the pathogenesis of RA, there is considerable interest in the evaluation of the synovium-specific effects of NFκB to unveil its potential for future therapeutic strategies. The goal is to evolve these strategies from the therapies that have a wide spectrum of effects and side effects into rheumatoid arthritis-specific therapies designed to inhibit distinct molecular pathways within the synovium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Baldwin AS Jr: The NF-_B and I-_B proteins: new discoveries and insights. Annu Rev Immunol 1996, 14:649–683.

    Article  PubMed  CAS  Google Scholar 

  2. PahlHL: Activators and target genes of Rel/NF_B transcription factors. Oncogene 1999, 18:6853–6866.

    Article  PubMed  CAS  Google Scholar 

  3. HandelML, McMorrowLB, GravalleseEM: NF_B in rheumatoid synovium: localization of p50 and p65. Arthritis Rheum 1995, 38:1762–1770.

    Article  PubMed  CAS  Google Scholar 

  4. AsaharaH, AsanumaM, OgawaN, NishibayashiS, InoueH:High DNA-binding activity of transcription factor NF_B in synovial membranes of patients with rheumatoid arthritis. Biochem Mol Biol Int 1995, 37:827–832.

    PubMed  CAS  Google Scholar 

  5. WakisakaS, SuzukiN, TakenoM, et al.: Involvement of simultaneous multiple transcription factor expression, including cAMP responsive element binding protein and OCT-1, for synovial cell outgrowth in patients with rheumatoid arthritis. Ann Rheum Dis 1998, 57:487–494.

    PubMed  CAS  Google Scholar 

  6. MarokR, WinyardPG, CoumbeA, et al.: Activation of the transcription factor nuclear factor _B in human inflamed synovial tissue. Arthritis Rheum 1996, 39:583–591.

    Article  PubMed  CAS  Google Scholar 

  7. DanningCL, IlleiGG, HitchonC, et al.: Macrophage-derived cytokine and nuclear factor _B p65 expression in synovial membrane and skin of patients with psoriatic arthritis. Arthritis Rheum 2000, 43:1244–1256.

    Article  PubMed  CAS  Google Scholar 

  8. StuhlmüllerB, UngethümU, ScholzeS, et al.: Identification of known and novel genes in activated monocytes from patients with rheumatoid arthritis. Arthritis Rheum 2000, 43:775–790.

    Article  PubMed  Google Scholar 

  9. NeumannE, KullmannF, JudexM, et al.: Identification of differentially expressed genes in rheumatoid arthritis by a combination of cDNA array and RAP-PCR. Arthritis Rheum 2002, 46:52–63.

    Article  PubMed  CAS  Google Scholar 

  10. TakPP, FiresteinGS: NF-_B: a key role in inflammatory diseases. J Clin Invest 2001, 107:7–11. Interesting review illustrating the numerous links of NF_B to the pathophysiology of inflammatory diseases.

    PubMed  CAS  Google Scholar 

  11. MakarovSS: NF-_B in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res 2001, 3:200–206. Well-written review focusing on the integration of NF_B into rheumatoid arthritis pathophysiology.

    Article  PubMed  CAS  Google Scholar 

  12. HofbauerLC, HeufelderAE: The role of osteoprotegerin and receptor activator of nuclear factor _B ligand in the pathogenesis and treatment of rheumatoid arthritis. Arthritis Rheum 2001, 44:253–259. The authors present a variety of novel ideas addressing the role of osteoprotegerin and its ligands in the molecular biology of rheumatoid arthritis.

    Article  PubMed  CAS  Google Scholar 

  13. AggarwalBB: Tumor necrosis factor receptor associated signalling molecules and their role in activation of apoptosis, JNK and NF-_B. Ann Rheum Dis 2000, 59:I6-I16.

    Article  PubMed  CAS  Google Scholar 

  14. FujisawaK, AonoH, HasunumaT, et al.: Activation of transcription factor NF_B in human synovial cells in response to tumor necrosis factor-_. Arthritis Rheum 1996, 39:197–203.

    Article  PubMed  CAS  Google Scholar 

  15. LehmannT, NguyenLQ, HandelML: Synovial fluid induced nuclear factor-_B DNA binding in a monocytic cell line. J Rheumatol 2000, 27:2769–2776.

    PubMed  CAS  Google Scholar 

  16. LawlorKE, CampbellIK, O’DonnellK, WuL, WicksIP:Molecular and cellular mediators of interleukin-1-dependent acute inflammatory arthritis. Arthritis Rheum 2001, 44:442–450. This article presents a link between interleukin-1, which is one of the driving molecules in rheumatoid joint destruction, and intracellular signaling involving the NF_B/Rel family.

    Article  PubMed  CAS  Google Scholar 

  17. CroffordLJ, TanB, McCarthyCJ, HlaT: Involvement of nuclear factor _B in the regulation of cyclooxygenase-2 expression by interleukin-1 in rheumatoid synoviocytes. Arthritis Rheum 1997, 40:226–236.

    Article  PubMed  CAS  Google Scholar 

  18. MiyazawaK, MoriA, YamamotoK, OkudairaH: Constitutive transcription of the human interleukin-6 gene by rheumatoid synoviocytes: spontaneous activation of NF-_B and CBF-1. Am J Pathol 1998, 152:793–803.

    PubMed  CAS  Google Scholar 

  19. MiyazawaK, MoriA, YamamotoK, OkudairaH:Transcriptional roles of CCAAT/enhancer binding protein-_ nuclear factor-_B, and C-promoter binding factor 1 in interleukin (IL)-1_-induced IL-6 synthesis by human rheumatoid fibroblast-like synoviocytes. J Biol Chem 1998, 273:7620–7627.

    Article  PubMed  CAS  Google Scholar 

  20. BondM, BakerAH, NewbyAC: NF-_B activity is essential for matrix metalloproteinase-1 and -3 upregulation in rabbit dermal fibroblasts. Biochem Biophys Res Commun 1999, 264:561–567.

    Article  PubMed  CAS  Google Scholar 

  21. VincentiMP, CoonCI, BrinckerhoffCE: NF_B/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1_ stimulated synovial fibroblasts. Arthritis Rheum 1998, 41:1987–1994.

    Article  PubMed  CAS  Google Scholar 

  22. AbeM, TanakaY, SaitoK, et al.: Regulation of interleukin (IL)-1_ gene transcription induced by IL-1_ in rheumatoid synovial fibroblast-like cells, E11, transformed with simian virus 40 large T antigen. J Rheumatol 1997, 24:420–429.

    PubMed  CAS  Google Scholar 

  23. AsamitsuK, SakuradaS, MashibaK, et al.: Alteration of the cellular response to interleukin-1_ by SV40 large T antigen in rheumatoid synovial fibroblasts. Arch Virol 1999, 144:317–327.

    Article  PubMed  CAS  Google Scholar 

  24. MiyazawaK, MoriA, OkudairaH: Establishment and characterization of a novel human rheumatoid fibroblast-like synoviocyte line, MH7A, immortalized with SV40T antigen. J Biochem 1998, 124:1153–1162.

    PubMed  CAS  Google Scholar 

  25. LiuY, WangY, YamakuchiM, et al.: Phosphoinositide-3 kinase-PKB/Akt pathway activation is involved in fibroblast Rat-1 transformation by human T-cell leukemia virus type I tax. Oncogene 2001, 20:2514–2526.

    Article  PubMed  CAS  Google Scholar 

  26. MaruyamaN, HiranoF, YoshikawaN, et al.: Thrombin stimulates cell proliferation in human fibroblast-like synoviocytes in nuclear factor-_B activation and protein kinase C mediated pathway. J Rheumatol 2000, 27:2777–2785.

    PubMed  CAS  Google Scholar 

  27. ShinH, KitajamaI, NakajimaT, et al.: Thrombin receptor mediated signals induce expressions of interleukin-6 and granulocyte colony stimulating factor via NF-_B activation in synovial fibroblasts. Ann Rheum Dis 1999, 58:55–60.

    Article  PubMed  CAS  Google Scholar 

  28. YoshidaS, KatohT, TetsukaT, et al.: Involvement of thioredoxin in rheumatoid arthritis: its costimulatory roles in the TNF-_-induced production of IL-6 and IL-8 from cultured synovial fibroblasts. J Immunol 1999, 163:351–358.

    PubMed  CAS  Google Scholar 

  29. MauriceMM, NakamuraH, GringhusS, et al.: Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis. Arthritis Rheum 1999, 42:2430–2439.

    Article  PubMed  CAS  Google Scholar 

  30. LiuR, O’ConnellM, JohnsonK, et al.: Extracellular signalregulated kinase 1/extracellular signal-regulated kinase 2 mitogen-activated protein kinase signaling and activation of activator protein 1 and nuclear factor _B transcription factors play central roles in interleukin-8 expression stimulated by monosodium urate monohydrate and calcium pyrophosphate crystals in monocytic cells. Arthritis Rheum 2000, 43:1145–1155. Chemotaxis contributes significantly to the accumulation of inflammatory cells in rheumatoid synovium. In this study, the authors provide evidence that expression of IL-8 depends on NF_B and other transcription factors in mononuclear phagocytes.

    Article  PubMed  CAS  Google Scholar 

  31. RomasE, BakharevskiO, HardsDK, et al.: Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis. Arthritis Rheum 2000, 43:821–826.

    Article  PubMed  CAS  Google Scholar 

  32. GravalleseEM, ManningC, TsayA, et al.: Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum 2000, 43:250–258. One of the first papers showing that osteoclast differentiation factor is expressed by RA synovial fibroblasts.

    Article  PubMed  CAS  Google Scholar 

  33. TakayanagiH, IizukaH, JujiT, et al.: Involvement of receptor activator of nuclear factor _B ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum 2000, 43:259–269. Bone destruction is one of the main features in rheumatoid arthritis pathophysiology; therefore, it is important to identify the molecular mechanisms involved in this process. The authors link receptor activator of nuclear factor κB ligand/osteoclast differentiation factor to this destructive process.

    Article  PubMed  CAS  Google Scholar 

  34. ShigeyamaY, PapT, KünzlerP, et al.: Expression of osteoclast differentiation factor in rheumatoid arthritis. Arthritis Rheum 2000, 43:2523–2530. Because the interaction between RANK and ODF appears to be crucial for bone degradation in RA synovium, it is important to localize and characterize (as performed in this study) the cells expressing ODF in RA synovium.

    Article  PubMed  CAS  Google Scholar 

  35. HaynesDR, CrottiTN, LoricM, et al.: Osteoprotegerin and receptor activator of nuclear factor-_B ligand (RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint. Rheumatology 2001, 40:623–630.

    Article  PubMed  CAS  Google Scholar 

  36. KotakeS, UdagawaN, HakodaM, et al.: Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients. Arthritis Rheum 2001, 44:1003–1012. An interesting study showing that T cells play a significant role in ODF-dependent bone destruction in RA.

    Article  PubMed  CAS  Google Scholar 

  37. SenM, ChamorroM, ReifertJ, CorrM, CarsonDA: Blockade of wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte activation. Arthritis Rheum 2001, 44:772–781. The wnt-5a/frizzled receptor-ligand pair is among the binding partners introduced most recently in RA pathophysiology. In this paper, the authors show that it is involved directly in RANKL-NF_B signaling.

    Article  PubMed  CAS  Google Scholar 

  38. SeiblR, BirchlerT, HossleJP, et al.: Expression of Toll-like receptor 2 in rheumatoid synovium. Arthritis Rheum 2000, 43:S161.

    Google Scholar 

  39. AupperleKR, BennettBL, BoyleDL, et al.: NF-_B regulation by I_B kinase in primary fibroblast-like synoviocytes. J Immunol 1999, 163:427–433. Regulation of NFκB by IκB is a key mechanism for most of the pathways involved in NFκB-dependent intracellular signaling. The experiments of this study show conclusively that this mechanism is also operative in rheumatoid arthritis synovial fibroblasts.

    PubMed  CAS  Google Scholar 

  40. YamasakiS, NakashimaT, NakamuraH, et al.: Importance of NF-_B in rheumatoid synovial tissues: in situ NF-_B expression and in vitro study using cultured synovial cells. Ann Rheum Dis 2001, 60:678–684.

    Article  PubMed  CAS  Google Scholar 

  41. AupperleKR, BennettBL, HanZ, et al.: NF-_B regulation by I_B kinase-2 in rheumatoid arthritis synoviocytes. J Immunol 2001, 166:2705–2711. Outstanding paper demonstrating that IKK-2-dominant negative mutant cell populations are resistant to TNFá-triggered NF_B nuclear translocation, whereas lack of IKK1 does not affect this mechanism.

    PubMed  CAS  Google Scholar 

  42. ZhangH-G, HuangN, LiuD, et al.: Gene therapy that inhibits nuclear translocation of nuclear factor _B results in tumor necrosis factor _-induced apoptosis of human synovial fibroblasts. Arthritis Rheum 2000, 43:1094–1105. The authors perform key gene therapy experiments unveiling central aspects of the role of NF_B in TNF-triggered apoptosis of rheumatoid synovial fibroblasts.

    Article  PubMed  CAS  Google Scholar 

  43. TakPP, GerlagDM, AupperleKR, et al.: Inhibitor of nuclear factor _B kinase _ is a key regulator of synovial inflammation. Arthritis Rheum 2001, 44:1897–1907. This study demonstrates that intra-articular gene transfer of wild-type IKKβ into normal rat joints can induce arthritis, whereas doublenegative IKKβ gene transfer considerably ameliorates the severity of adjuvant arthritis.

    Article  PubMed  CAS  Google Scholar 

  44. BondesonJ, FoxwellB, BrennanF, FeldmannM: Defining therapeutic targets by using adenovirus: blocking NF-_B inhibits both inflammatory and destructive mechanisms in rheumatoid synovium but spares anti-inflammatory mediators. Proc Natl Acad Sci U S A 1999, 96:5668–5673.

    Article  PubMed  CAS  Google Scholar 

  45. TakayanagiH, OgasawaraK, HisaS, et al.: T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-_. Nature 2000, 408:535–536. Interferon-gamma is among the molecules that are capable of down-regulating NF_B activity. The authors show that interferon-gamma was able to degrade tumor necrosis factor receptor-associated factor 6 followed by down-regulation of RANKL-induced activation of NF_B.

    Article  Google Scholar 

  46. Abu-AmerY: IL-4 abrogates osteoclastogenesis through STAT6-dependent inhibition of NF-_B. J Clin Invest 2001, 107:1375–1385. The study demonstrates that interleukin-4, an important inhibitor molecule in rheumatoid arthritis synovium, blocks NF_B transactivation through its intracellular second messenger STAT6/IL-4 STAT.

    PubMed  CAS  Google Scholar 

  47. KawahitoY, KondoM, TsubouchiY, et al.: 15-deoxydelta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats. J Clin Invest 2000, 106:189–197. Peroxisome proliferator-activated receptors, which are known to be central molecules in glucose metabolism, may be important messenger molecules in rheumatoid arthritis. In this excellent study, the authors show that PPARs most likely play a substantial role in rheumatoid joint destruction.

    PubMed  CAS  Google Scholar 

  48. LembergerT, DesvergneB, WahliW: Peroxisome proliferator activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol 1996, 12:335–363.

    Article  PubMed  CAS  Google Scholar 

  49. FahmiH, Di Battista JA, PelletierJ-P, et al.: Peroxisome proliferator-activated receptor _ activators inhibit interleukin-1_-induced nitric oxide and matrix metalloproteinase 13 production in human chondrocytes. Arthritis Rheum 2001, 44:595–607. The authors present cutting-edge data on the effects of PPARs on interleukin-1-mediated matrix metalloproteinase production in chondrocytes.

    Article  PubMed  CAS  Google Scholar 

  50. PapT, FranzJK, HummelKM, et al.: Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction. Arthritis Res 2000, 2:59–64. Down-regulation of proliferation inhibitors contributes to the progressive growth of rheumatoid arthritis synovium. The authors show that down-regulation of the tumor suppressor may be one of these crucial mechanisms.

    Article  PubMed  CAS  Google Scholar 

  51. GustinJA, MaehamaT, DixonJE, DonnerDB: The PTEN tumor suppressor protein inhibits tumor necrosis factor-induced nuclear factor-_B activity. J Biol Chem 2001, 276:27740–27744. A concise paper illustrating the relationship between the tumor suppressor PTEN, TNF, and activity of NF_B.

    Article  PubMed  CAS  Google Scholar 

  52. KoulD, YaoY, AbbruzzeseJL, YungWK, ReddySA: Tumor suppressor MMAC/PTEN inhibits cytokine-induced NF_B activation without interfering with the I_B degradation pathway. J Biol Chem 2001, 276:11402–11408. The authors present excellent data that show that additional NF_B regulatory mechanisms bypassing I_B exist and are modulated by the tumor suppressor PTEN.

    Article  PubMed  CAS  Google Scholar 

  53. PianettiS, ArsuraM, Romieu-MourezR, CoffeyRJ, SonensheinGE: Her-2/neu overexpression induces NF-_B via a PI3-kinase/Akt pathway involving calpain-mediated degradation of I_B-_ that can be inhibited by the tumor suppressor PTEN. Oncogene 2001, 20:1287–1299. One of the few papers in this field that provide evidence for the interacting mechanisms around NFκB involving various signaling molecules such as akt-1 and PTEN.

    Article  PubMed  CAS  Google Scholar 

  54. BondesonJ, BrennanF, FixwellB, FeldmannM: Effective adenoviral transfer of I_B_ into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-_ dependent. J Rheumatol 2000, 27:2078–2089. Important gene therapy study illustrating by proof-of-principle that induction of matrix metalloproteinases and cytokines is NF_B-dependent.

    PubMed  CAS  Google Scholar 

  55. AzumaM, AotaK, TamataniT, et al.: Suppression of tumor necrosis factor _-induced matrix metalloproteinase 9 production by the introduction of a super-repressor form of inhibitor of nuclear factor _B_ complementary DNA into immortalized human salivary gland acinar cells: prevention of the destruction of the acinar structure in Sjögren’s syndrome salivary glands. Arthritis Rheum 2000, 43:1756–1767.

    Article  PubMed  CAS  Google Scholar 

  56. JovanovicD, Di Battista JA, Martel-PelletierJ, et al.: Modulation of TIMP-1 synthesis by antiinflammatory cytokines and prostaglandin E2 in interleukin-17 stimulated human monocytes/macrophages. J Rheumatol 2001, 28:712–718.

    PubMed  CAS  Google Scholar 

  57. MengsholJA, VincentiMP, CoonCI, BarchowskyA, BrinckerhoffCE: Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-jun N-terminal kinase, and nuclear factor _B: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum 2000, 43:801–811. The data of this study reveal that NF_B, among other intracellular signaling molecules, is involved directly in IL-1-triggered matrix metalloproteinase synthesis.

    Article  PubMed  CAS  Google Scholar 

  58. CarlosTM, HarlanJM: Leukocyte-endothelial adhesion molecules. Blood 1994, 84:2068–2101.

    PubMed  CAS  Google Scholar 

  59. CarterRA, WicksIP: Vascular cell adhesion molecule 1 (CD106): a multifaceted regulator of joint inflammation. Arthritis Rheum 2001, 44:985–994.

    Article  PubMed  CAS  Google Scholar 

  60. KriegsmannJ, KeyszerGM, GeilerT, et al.: Expression of vascular cell adhesion molecule-1 mRNA and protein in rheumatoid synovium demonstrated by in situ hybridization and immunohistochemistry. Lab Invest 1995, 72:209–214.

    PubMed  CAS  Google Scholar 

  61. LiP, SanzI, O’KeefeRJ, SchwarzEM: NF-_B regulates VCAM-1 expression on fibroblast-like synoviocytes. J Immunol 2000, 164:5990–5997. Because adhesion mechanisms are important for cellular interactions in rheumatoid joints, this paper contributes significantly to the understanding of regulation of the expression of the adhesion molecule VCAM-1, which appears to be among the most important RA-associated adhesion molecules.

    PubMed  CAS  Google Scholar 

  62. BoumpasDT: A novel action of glucocorticoids—NF_B inhibition. Br J Rheumatol 1996, 35:709–710.

    Article  PubMed  CAS  Google Scholar 

  63. YoshidaS, KatoT, SakuradaS, et al.: Inhibition of IL-6 and IL-8 induction from cultured rheumatoid synovial fibroblasts by treatment with aurothioglucose. Int Immunol 1999, 11:151–158.

    Article  PubMed  CAS  Google Scholar 

  64. VollRE, DechantC, BöttcherA, et al.: Decrease of NF-_B DNA-binding activity in peripheral blood mononuclear cells after treatment of rheumatoid arthritis with anti-TNF antibody infliximab. Arthritis Rheum 2000, 43:S277.

    Google Scholar 

  65. WahlC, LiptayS, AdlerG, SchmidRM: Sulfasalazine: a potent and specific inhibitor of NF_B. J Clin Invest 1998, 101:1163–1174.

    Article  PubMed  CAS  Google Scholar 

  66. MannaSK, AggarwalBB: Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent NF-_B activation and gene expression. J Immunol 1999, 162:2095–2102. Well-presented study reflecting some of the molecular mechanisms that are responsible for the beneficial effects of the novel immunosuppressive agent leflunomide, which has recently been introduced in the RA treatment armamentarium.

    PubMed  CAS  Google Scholar 

  67. BreedveldFC, DayerJM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis 2000, 59:841–849.

    Article  PubMed  CAS  Google Scholar 

  68. NiederbergerE, TegederI, VetterG, et al.: Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF-_B. FASEB J 2001, 15:1622–1624. The study shows important data in a bench-to-bedside approach that may be helpful for interpretation of celecoxib-dependent side effects.

    PubMed  CAS  Google Scholar 

  69. MiagkovAV, KovalenkoDV, BrownCE, et al.: NF-_B activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc Natl Acad Sci U S A 1998, 95:13859–13864.

    Article  PubMed  CAS  Google Scholar 

  70. PettitAR, MacDonaldKPA, O’SullivanB, ThomasR:Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates. Arthritis Rheum 2000, 43:791–800. An important study revealing the origin and localization of nuclear RelB transcription factor in rheumatoid synovial tissue.

    Article  PubMed  CAS  Google Scholar 

  71. YoshimuraS, BondesonJ, BrennanFM, FoxwellBM, FeldmannM: Role of NF_B in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with the proteasome inhibitor PSI. Eur J Immunol 2001, 31:1883–1893. This paper may provide the basis for a novel NF_B-targeted treatment approach in RA, targeting proteasome-associated antigen presentation of dendritic cells.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany

    Ulf Müller-Ladner MD

Authors
  1. Ulf Müller-Ladner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renate E. Gay MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Steffen Gay MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Müller-Ladner, U., Gay, R.E. & Gay, S. Role of nuclear factor κb in synovial inflammation. Curr Rheumatol Rep 4, 201–207 (2002). https://doi.org/10.1007/s11926-002-0066-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-002-0066-1

Keywords

Search

Navigation