nach oben

Erschienen in:

11.01.2018 | Original Paper

IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells

verfasst von: Hatem A. Elshabrawy, Michael V. Volin, Abdul B. Essani, Zhenlong Chen, Iain B. McInnes, Katrien Van Raemdonck, Karol Palasiewicz, Shiva Arami, Mark Gonzalez, Hossam M. Ashour, Seung-jae Kim, Guofei Zhou, David A. Fox, Shiva Shahrara

Erschienen in: Angiogenesis | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11Rα in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues. Since IL-11Rα was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11Rα strongly provoked fibroblast infiltration into RA joint, while cell proliferation was unaffected by this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was responsible for the indirect effect of IL-11 on endothelial cell transmigration and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit endothelial cell transmigration and tube formation. We conclude that IL-11 binding to endothelial IL-11Rα can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.

Heinrich PC, Behrmann I, Haan S et al (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20CrossRefPubMedPubMedCentral

Putoczki TL, Thiem S, Loving A et al (2013) Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell 24:257–271CrossRefPubMed

Paul SR, Bennett F, Calvetti JA et al (1990) Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci USA 87:7512–7516CrossRefPubMedPubMedCentral

Paul SR, Yang YC, Donahue RE et al (1991) Stromal cell-associated hematopoiesis: immortalization and characterization of a primate bone marrow-derived stromal cell line. Blood 77:1723–1733PubMed

Du X, Williams DA (1997) Interleukin-11: review of molecular, cell biology, and clinical use. Blood 89:3897–3908PubMed

Xu DH, Zhu Z, Wakefield MR et al (2016) The role of IL-11 in immunity and cancer. Cancer Lett 373:156–163CrossRefPubMed

Quesniaux VF, Clark SC, Turner K et al (1992) Interleukin-11 stimulates multiple phases of erythropoiesis in vitro. Blood 80:1218–1223PubMed

Jacobsen SE, Okkenhaug C, Veiby OP et al (1994) Interleukin 13: novel role in direct regulation of proliferation and differentiation of primitive hematopoietic progenitor cells. J Exp Med 180:75–82CrossRefPubMed

Orazi A, Cooper RJ, Tong J et al (1996) Effects of recombinant human interleukin-11 (Neumega rhIL-11 growth factor) on megakaryocytopoiesis in human bone marrow. Exp Hematol 24:1289–1297PubMed

10.

Putoczki T, Ernst M (2010) More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer. J Leukoc Biol 88:1109–1117CrossRefPubMed

11.

Taniguchi K, Karin M (2014) IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Semin Immunol 26:54–74CrossRefPubMed

12.

Yoshizaki A, Nakayama T, Yamazumi K et al (2006) Expression of interleukin (IL)-11 and IL-11 receptor in human colorectal adenocarcinoma: IL-11 up-regulation of the invasive and proliferative activity of human colorectal carcinoma cells. Int J Oncol 29:869–876PubMed

13.

Yamazumi K, Nakayama T, Kusaba T et al (2006) Expression of interleukin-11 and interleukin-11 receptor alpha in human colorectal adenocarcinoma; immunohistochemical analyses and correlation with clinicopathological factors. World J Gastroenterol 12:317–321CrossRefPubMedPubMedCentral

14.

Zhang X, Tao Y, Chopra M et al (2015) IL-11 induces Th17 cell responses in patients with early relapsing-remitting multiple sclerosis. J Immunol 194:5139–5149CrossRefPubMed

15.

Walmsley M, Butler DM, Marinova-Mutafchieva L et al (1998) An anti-inflammatory role for interleukin-11 in established murine collagen-induced arthritis. Immunology 95:31–37CrossRefPubMedPubMedCentral

16.

Wong PK, Campbell IK, Robb L et al (2005) Endogenous IL-11 is pro-inflammatory in acute methylated bovine serum albumin/interleukin-1-induced (mBSA/IL-1)arthritis. Cytokine 29:72–76CrossRefPubMed

17.

Chung SJ, Kwon YJ, Park MC et al (2011) The correlation between increased serum concentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J 52:113–120CrossRefPubMed

18.

Moreland L, Gugliotti R, King K et al (2001) Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis. Arthritis Res 3:247–252CrossRefPubMedPubMedCentral

19.

Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheumatol 31:315–324CrossRef

20.

Pickens SR, Chamberlain ND, Volin MV et al (2011) Characterization of CCL19 and CCL21 in rheumatoid arthritis. Arthritis Rheumatol 63:914–922CrossRef

21.

Pickens SR, Chamberlain ND, Volin MV et al (2011) Characterization of interleukin-7 and interleukin-7 receptor in the pathogenesis of rheumatoid arthritis. Arthritis Rheumatol 63:2884–2893CrossRef

22.

Chamberlain ND, Vila OM, Volin MV et al (2012) TLR5, a novel and unidentified inflammatory mediator in rheumatoid arthritis that correlates with disease activity score and joint TNF-alpha levels. J Immunol 189:475–483CrossRefPubMedPubMedCentral

23.

Kim SJ, Chen Z, Essani AB, Elshabrawy HA, Volin MV, Volkov S, Swedler W, Arami S, Sweiss N, Shahrara S (2015) Identification of a novel TLR7 endogenous ligand in RA synovial fluid that can provoke arthritic joint inflammation. Arthritis Rheumatol 68(5):1099–1110. https://doi.org/10.1002/art.39544

24.

Chen Z, Kim SJ, Chamberlain ND et al (2013) The novel role of IL-7 ligation to IL-7 receptor in myeloid cells of rheumatoid arthritis and collagen-induced arthritis. J Immunol 190:5256–5266CrossRefPubMedPubMedCentral

25.

Shahrara S, Pickens SR, Mandelin AM 2nd et al (2010) IL-17-mediated monocyte migration occurs partially through CC chemokine ligand 2/monocyte chemoattractant protein-1 induction. J Immunol 184:4479–4487CrossRefPubMedPubMedCentral

26.

Morgan R, Endres J, Behbahani-Nejad N et al (2015) Expression and function of aminopeptidase N/CD13 produced by fibroblast-like synoviocytes in rheumatoid arthritis: role of CD13 in chemotaxis of cytokine-activated T cells independent of enzymatic activity. Arthritis Rheumatol 67:74–85CrossRefPubMedPubMedCentral

27.

Curtis DJ, Hilton DJ, Roberts B et al (1997) Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist. Blood 90:4403–4412PubMed

28.

Ota F, Maeshima A, Yamashita S et al (2003) Activin A induces cell proliferation of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Rheumatol 48:2442–2449CrossRef

29.

Pickens SR, Volin MV, Mandelin AM 2nd et al (2010) IL-17 contributes to angiogenesis in rheumatoid arthritis. J Immunol 184:3233–3241CrossRefPubMedPubMedCentral

30.

Pickens SR, Chamberlain ND, Volin MV et al (2012) Role of the CCL21 and CCR7 pathways in rheumatoid arthritis angiogenesis. Arthritis Rheumatol 64:2471–2481CrossRef

31.

Chen Z, Kim SJ, Essani AB et al (2015) Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis. Ann Rheum Dis 74:1898–1906CrossRefPubMed

32.

Lefevre S, Knedla A, Tennie C et al (2009) Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med 15:1414–1420CrossRefPubMedPubMedCentral

33.

Bartok B, Firestein GS (2010) Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev 233:233–255CrossRefPubMedPubMedCentral

34.

Elshabrawy HA, Chen Z, Volin MV et al (2015) The pathogenic role of angiogenesis in rheumatoid arthritis. Angiogenesis 18:433–448CrossRefPubMedPubMedCentral

35.

Taki H, Sugiyama E, Mino T et al (1998) Differential inhibitory effects of indomethacin, dexamethasone, and interferon-gamma (IFN-gamma) on IL-11 production by rheumatoid synovial cells. Clin Exp Immunol 112:133–138CrossRefPubMedPubMedCentral

36.

Taki H, Sugiyama E, Kuroda A et al (2000) Interleukin-4 inhibits interleukin-11 production by rheumatoid synovial cells. Rheumatology (Oxford) 39:728–731CrossRef

37.

Mino T, Sugiyama E, Taki H et al (1998) Interleukin-1 alpha and tumor necrosis factor alpha synergistically stimulate prostaglandin E2-dependent production of interleukin-11 in rheumatoid synovial fibroblasts. Arthritis Rheumatol 41:2004–2013CrossRef

38.

Okamoto H, Yamamura M, Morita Y et al (1997) The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. Arthritis Rheumatol 40:1096–1105CrossRef

39.

Trontzas P, Kamper EF, Potamianou A et al (1998) Comparative study of serum and synovial fluid interleukin-11 levels in patients with various arthritides. Clin Biochem 31:673–679CrossRefPubMed

40.

Hermann JA, Hall MA, Maini RN et al (1998) Important immunoregulatory role of interleukin-11 in the inflammatory process in rheumatoid arthritis. Arthritis Rheumatol 41:1388–1397CrossRef

41.

Yamashita A, Yonemitsu Y, Okano S et al (2002) Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats. J Immunol 168:450–457CrossRefPubMed

42.

Koch AE, Kunkel SL, Shah MR et al (1995) Growth-related gene product alpha. A chemotactic cytokine for neutrophils in rheumatoid arthritis. J Immunol 155:3660–3666PubMed

43.

Koch AE, Kunkel SL, Harlow LA et al (1994) Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis. J Clin Invest 94:1012–1018CrossRefPubMedPubMedCentral

44.

Girasole G, Passeri G, Jilka RL et al (1994) Interleukin-11: a new cytokine critical for osteoclast development. J Clin Invest 93:1516–1524CrossRefPubMedPubMedCentral

45.

Yin TG, Schendel P, Yang YC (1992) Enhancement of in vitro and in vivo antigen-specific antibody responses by interleukin 11. J Exp Med 175:211–216CrossRefPubMed

46.

Trepicchio WL, Bozza M, Pedneault G et al (1996) Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J Immunol 157:3627–3634PubMed

47.

Trepicchio WL, Wang L, Bozza M et al (1997) IL-11 regulates macrophage effector function through the inhibition of nuclear factor-kappaB. J Immunol 159:5661–5670PubMed

48.

Lee SY, Kwok SK, Son HJ et al (2013) IL-17-mediated Bcl-2 expression regulates survival of fibroblast-like synoviocytes in rheumatoid arthritis through STAT3 activation. Arthritis Res Ther 15:R31CrossRefPubMedPubMedCentral

49.

Xing R, Yang L, Jin Y et al (2016) Interleukin-21 induces proliferation and proinflammatory cytokine profile of fibroblast-like synoviocytes of patients with rheumatoid arthritis. Scand J Immunol 83:64–71CrossRefPubMed

50.

Zhu J, Jia E, Zhou Y et al (2015) Interleukin-22 secreted by NKp44+ natural killer cells promotes proliferation of fibroblast-like synoviocytes in rheumatoid arthritis. Medicine (Baltimore) 94:e2137CrossRef

51.

Calmon-Hamaty F, Combe B, Hahne M et al (2011) Lymphotoxin alpha stimulates proliferation and pro-inflammatory cytokine secretion of rheumatoid arthritis synovial fibroblasts. Cytokine 53:207–214CrossRefPubMed

52.

Elias JA, Zheng T, Whiting NL et al (1994) IL-1 and transforming growth factor-beta regulation of fibroblast-derived IL-11. J Immunol 152:2421–2429PubMed

53.

Guo X, Pan Y, Xiao C et al (2012) Fractalkine stimulates cell growth and increases its expression via NF-kappaB pathway in RA-FLS. Int J Rheum Dis 15:322–329CrossRefPubMed

54.

Garcia-Vicuna R, Gomez-Gaviro MV, Dominguez-Luis MJ et al (2004) CC and CXC chemokine receptors mediate migration, proliferation, and matrix metalloproteinase production by fibroblast-like synoviocytes from rheumatoid arthritis patients. Arthritis Rheumatol 50:3866–3877CrossRef

55.

Edhayan G, Ohara RA, Stinson WA et al (2016) Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in rheumatoid arthritis. Arthritis Res Ther 18:87CrossRefPubMedPubMedCentral

Titel: IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells
verfasst von: Hatem A. Elshabrawy
Michael V. Volin
Abdul B. Essani
Zhenlong Chen
Iain B. McInnes
Katrien Van Raemdonck
Karol Palasiewicz
Shiva Arami
Mark Gonzalez
Hossam M. Ashour
Seung-jae Kim
Guofei Zhou
David A. Fox
Shiva Shahrara
Publikationsdatum: 11.01.2018
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 2/2018
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-017-9589-y

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target

Soluble delta-like 1 homolog (DLK1) stimulates angiogenesis through Notch1/Akt/eNOS signaling in endothelial cells

Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism

Serum/glucocorticoid-regulated kinase 1 as a novel transcriptional target of bone morphogenetic protein-ALK1 receptor signaling in vascular endothelial cells

Somatic NRAS mutation in patient with generalized lymphatic anomaly