C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene

A. C. Bakker, F. A J Van De Loo, L. A B Joosten, O. J. Arntz, A. W. Varley, R. S. Munford, W. B. Van Den Berg

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective. To achieve disease-inducible expression of recombinant antiinflammatory proteins in order to allow autoregulation of drug dose by natural homeostatic mechanisms. Methods. We compared the inducible 2-component expression system (C3-human immunode-ficiency virus/transactivator of transcription [C3-Tat/ H/V]) with the constitutive cytomegalovirus (CMV) promoter in the polyarticular collagen-induced arthritis (CIA) model in mice. DBA/1 mice were immunized with bovine type H collagen and were given boosters on day 21. On day 22, mice were injected intraarticularly with the adenoviral vectors AdCMVLuc, AdCMVhIL-1Ra, AdC3-Tat/HIV-Luc, or AdC3-Tat/H/V-hIL-1Ra. The injected knee joints and hind paws were then scored for signs of arthritis, and knee joint histology was compared. Results. The CMV-driven interleukin-1 receptor antagonist (IL-1Ra) expression resulted in a high constitutive expression and amelioration of CIA. C3-Tat/ HIV-driven IL-1Ra expression could be detected only on days 24, 29, and 35. Fourteen days after injection of the vectors, CIA was significantly better inhibited by the C3-Tat/HIV-driven IL-1Ra expression compared with the CMV-driven IL-1Ra expression. Moreover, prevention of CIA in the knee joints also prevented CIA in the untreated hind paws. Conclusion. Our data demonstrate for the first time the feasibility of an inducible expression system for local production of IL-1Ra for treatment of arthritis in the CIA model.

Original languageEnglish (US)
Pages (from-to)1661-1670
Number of pages10
JournalArthritis and Rheumatism
Volume46
Issue number6
DOIs
StatePublished - 2002

Fingerprint

Experimental Arthritis
Interleukin-1 Receptors
Cytomegalovirus
Transgenes
Genetic Therapy
HIV
Knee Joint
Arthritis
Inbred DBA Mouse
Trans-Activators
Recombinant Proteins
Histology
Homeostasis
Anti-Inflammatory Agents
Collagen
Viruses
Injections
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene. / Bakker, A. C.; Van De Loo, F. A J; Joosten, L. A B; Arntz, O. J.; Varley, A. W.; Munford, R. S.; Van Den Berg, W. B.

In: Arthritis and Rheumatism, Vol. 46, No. 6, 2002, p. 1661-1670.

Research output: Contribution to journalArticle

Bakker, A. C. ; Van De Loo, F. A J ; Joosten, L. A B ; Arntz, O. J. ; Varley, A. W. ; Munford, R. S. ; Van Den Berg, W. B. / C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene. In: Arthritis and Rheumatism. 2002 ; Vol. 46, No. 6. pp. 1661-1670.
@article{bb41f95425904c4aac245470dbcf1277,
title = "C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene",
abstract = "Objective. To achieve disease-inducible expression of recombinant antiinflammatory proteins in order to allow autoregulation of drug dose by natural homeostatic mechanisms. Methods. We compared the inducible 2-component expression system (C3-human immunode-ficiency virus/transactivator of transcription [C3-Tat/ H/V]) with the constitutive cytomegalovirus (CMV) promoter in the polyarticular collagen-induced arthritis (CIA) model in mice. DBA/1 mice were immunized with bovine type H collagen and were given boosters on day 21. On day 22, mice were injected intraarticularly with the adenoviral vectors AdCMVLuc, AdCMVhIL-1Ra, AdC3-Tat/HIV-Luc, or AdC3-Tat/H/V-hIL-1Ra. The injected knee joints and hind paws were then scored for signs of arthritis, and knee joint histology was compared. Results. The CMV-driven interleukin-1 receptor antagonist (IL-1Ra) expression resulted in a high constitutive expression and amelioration of CIA. C3-Tat/ HIV-driven IL-1Ra expression could be detected only on days 24, 29, and 35. Fourteen days after injection of the vectors, CIA was significantly better inhibited by the C3-Tat/HIV-driven IL-1Ra expression compared with the CMV-driven IL-1Ra expression. Moreover, prevention of CIA in the knee joints also prevented CIA in the untreated hind paws. Conclusion. Our data demonstrate for the first time the feasibility of an inducible expression system for local production of IL-1Ra for treatment of arthritis in the CIA model.",
author = "Bakker, {A. C.} and {Van De Loo}, {F. A J} and Joosten, {L. A B} and Arntz, {O. J.} and Varley, {A. W.} and Munford, {R. S.} and {Van Den Berg}, {W. B.}",
year = "2002",
doi = "10.1002/art.10481",
language = "English (US)",
volume = "46",
pages = "1661--1670",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene

AU - Bakker, A. C.

AU - Van De Loo, F. A J

AU - Joosten, L. A B

AU - Arntz, O. J.

AU - Varley, A. W.

AU - Munford, R. S.

AU - Van Den Berg, W. B.

PY - 2002

Y1 - 2002

N2 - Objective. To achieve disease-inducible expression of recombinant antiinflammatory proteins in order to allow autoregulation of drug dose by natural homeostatic mechanisms. Methods. We compared the inducible 2-component expression system (C3-human immunode-ficiency virus/transactivator of transcription [C3-Tat/ H/V]) with the constitutive cytomegalovirus (CMV) promoter in the polyarticular collagen-induced arthritis (CIA) model in mice. DBA/1 mice were immunized with bovine type H collagen and were given boosters on day 21. On day 22, mice were injected intraarticularly with the adenoviral vectors AdCMVLuc, AdCMVhIL-1Ra, AdC3-Tat/HIV-Luc, or AdC3-Tat/H/V-hIL-1Ra. The injected knee joints and hind paws were then scored for signs of arthritis, and knee joint histology was compared. Results. The CMV-driven interleukin-1 receptor antagonist (IL-1Ra) expression resulted in a high constitutive expression and amelioration of CIA. C3-Tat/ HIV-driven IL-1Ra expression could be detected only on days 24, 29, and 35. Fourteen days after injection of the vectors, CIA was significantly better inhibited by the C3-Tat/HIV-driven IL-1Ra expression compared with the CMV-driven IL-1Ra expression. Moreover, prevention of CIA in the knee joints also prevented CIA in the untreated hind paws. Conclusion. Our data demonstrate for the first time the feasibility of an inducible expression system for local production of IL-1Ra for treatment of arthritis in the CIA model.

AB - Objective. To achieve disease-inducible expression of recombinant antiinflammatory proteins in order to allow autoregulation of drug dose by natural homeostatic mechanisms. Methods. We compared the inducible 2-component expression system (C3-human immunode-ficiency virus/transactivator of transcription [C3-Tat/ H/V]) with the constitutive cytomegalovirus (CMV) promoter in the polyarticular collagen-induced arthritis (CIA) model in mice. DBA/1 mice were immunized with bovine type H collagen and were given boosters on day 21. On day 22, mice were injected intraarticularly with the adenoviral vectors AdCMVLuc, AdCMVhIL-1Ra, AdC3-Tat/HIV-Luc, or AdC3-Tat/H/V-hIL-1Ra. The injected knee joints and hind paws were then scored for signs of arthritis, and knee joint histology was compared. Results. The CMV-driven interleukin-1 receptor antagonist (IL-1Ra) expression resulted in a high constitutive expression and amelioration of CIA. C3-Tat/ HIV-driven IL-1Ra expression could be detected only on days 24, 29, and 35. Fourteen days after injection of the vectors, CIA was significantly better inhibited by the C3-Tat/HIV-driven IL-1Ra expression compared with the CMV-driven IL-1Ra expression. Moreover, prevention of CIA in the knee joints also prevented CIA in the untreated hind paws. Conclusion. Our data demonstrate for the first time the feasibility of an inducible expression system for local production of IL-1Ra for treatment of arthritis in the CIA model.

UR - http://www.scopus.com/inward/record.url?scp=0036277184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036277184&partnerID=8YFLogxK

U2 - 10.1002/art.10481

DO - 10.1002/art.10481

M3 - Article

C2 - 12115199

AN - SCOPUS:0036277184

VL - 46

SP - 1661

EP - 1670

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 6

ER -