Research article

The Presence of Interleukin 18 Binding Protein Isoforms in Chinese Patients with Rheumatoid Arthritis

  • Received: 06 January 2016 Accepted: 16 February 2016 Published: 25 February 2016
  •  Objective: Human IL-18BP gene encodes at least four distinct isoforms (IL18BPa-d) derived by alternative splicing. Their presence in RA local inflammation is not yet examined. This study aimed to determine the messenger transcript and protein levels of IL-18BP isoforms in patients with Rheumatoid Arthritis (RA). Materials: The study comprises 65 rheumatic patients, 22 Osteoarthritis (OA), and 40 sex and age matched normal controls (NC). Peripheral blood mononuclear cells (PBMCs) and synovial fluids mononuclear cells (SFMCs) were prepared by using Ficoll-Hypaque procedure. The expression and presence of different isoforms were determined by using real-time PCR and ELISA respectively. Results: IL-18BP messenger transcript has been extremely expressed in synovial fluids (SF) and synovial tissues (ST) of RA patients compared to OA patients (p < 0.001). IL-18BP auto-antibodies were noticed in RA plasma and SF (41.7%; 37.9%), in OA-SF (9.0%), and in plasma of NC (4.0%). Comparable to different isoforms, isoform “c” showed significant local expression (p < 0.001) in RA-SFMC and systematic expression (p < 0.001) between RA- and NC-PBMCs, isoform “a” was least expressed. Isoform “c” and “d” proteins were solely detected by western blot in RA. Conclusions: This study emphasizes the local existence of isoform “c” and “d”, and the possible presence of autoantibodies against IL-18BPa in RA patients, which made a pea for further investigation, putting in place their actual role.

    Citation: K.E. Khalid, Hamdi Nouri Nsairat, Jingwu Z. Zhang. The Presence of Interleukin 18 Binding Protein Isoforms in Chinese Patients with Rheumatoid Arthritis[J]. AIMS Medical Science, 2016, 3(1): 103-113. doi: 10.3934/medsci.2016.1.103

    Related Papers:

  •  Objective: Human IL-18BP gene encodes at least four distinct isoforms (IL18BPa-d) derived by alternative splicing. Their presence in RA local inflammation is not yet examined. This study aimed to determine the messenger transcript and protein levels of IL-18BP isoforms in patients with Rheumatoid Arthritis (RA). Materials: The study comprises 65 rheumatic patients, 22 Osteoarthritis (OA), and 40 sex and age matched normal controls (NC). Peripheral blood mononuclear cells (PBMCs) and synovial fluids mononuclear cells (SFMCs) were prepared by using Ficoll-Hypaque procedure. The expression and presence of different isoforms were determined by using real-time PCR and ELISA respectively. Results: IL-18BP messenger transcript has been extremely expressed in synovial fluids (SF) and synovial tissues (ST) of RA patients compared to OA patients (p < 0.001). IL-18BP auto-antibodies were noticed in RA plasma and SF (41.7%; 37.9%), in OA-SF (9.0%), and in plasma of NC (4.0%). Comparable to different isoforms, isoform “c” showed significant local expression (p < 0.001) in RA-SFMC and systematic expression (p < 0.001) between RA- and NC-PBMCs, isoform “a” was least expressed. Isoform “c” and “d” proteins were solely detected by western blot in RA. Conclusions: This study emphasizes the local existence of isoform “c” and “d”, and the possible presence of autoantibodies against IL-18BPa in RA patients, which made a pea for further investigation, putting in place their actual role.


    加载中
    [1] Buckley CD (1997) Treatment of rheumatoid arthritis. Science, medicine and future. BMJ 315: 236-238.
    [2] Novick D, Kim SH, Fantuzzi G, et al. (1999) Interleukin-18 binding protein: novel modulator of the Th1 cytokine response. Immunity 10: 127-136. doi: 10.1016/S1074-7613(00)80013-8
    [3] Szekanecz Z, Kim J, Koch AE (2003) Chemokines and chemokine receptors in rheumatoid arthritis. Semin Immunol 15: 15-21.
    [4] Kim SH, Eisenstein M, Reznikov L, et al. (2000) Structural requirements of six naturally occurring isoforms of the IL-18 binding protein to inhibit IL-18. Proc Natl Acad Sci USA 97: 1190-1195. doi: 10.1073/pnas.97.3.1190
    [5] Arend WP, Malyak M, Smith MF, et al. (1994) Binding of IL-1α, IL-1β, and IL-1 receptor antagonist by soluble IL-1 receptors and levels of soluble IL-1 receptors in synovial fluids. J Immunol 153: 4766-4774.
    [6] Terlizzese M, Simoni P, Antonetti F (1996) In vitro comparison of inhibiting ability of soluble TNF receptor p75 (TBP II) vs. soluble TNF receptor p55 (TBP I) against TNF-alpha and
    TNF-beta. J Interferon Cytokine Res 16:1047-1053.
    [7] Bresnihan B, Roux-Lombard P, Murphy E, et al. (2002) Serum interleukin 18 and interleukin 18 binding protein in rheumatoid arthritis. Ann Rheum Dis 61: 726-729.
    [8] Yamamura M, Kawashima M, Taniai M, et al. (2001) Interferon-γ inducing activity of interleukin- 18 in the joint with rheumatoid arthritis. Arthritis Rheum 44: 275-285. doi: 10.1002/1529-0131(200102)44:2<275::AID-ANR44>3.0.CO;2-B
    [9] Corbaz A, ten Hove T, Herren S, et al. (2002) IL-18-binding protein expression by endothelial cells and macrophages is up-regulated during active Crohn's disease. J Immunol 168: 3608-3616.
    [10] Kumar S, McDonnell PC, Lehr R, et al. (2000) Identification and initial characterization of four novel members of the interleukin- 1 family. J Biol Chem 275: 10308-10314. doi: 10.1074/jbc.275.14.10308
    [11] Pan GH, Risser P, Mao WG, et al. (2001) IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp. Cytokine 13: 1-7. doi: 10.1006/cyto.2000.0799
  • Reader Comments
  • © 2016 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(5241) PDF downloads(1168) Cited by(2)

Article outline

Figures and Tables

Figures(3)  /  Tables(2)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog