GV1001 immunotherapy ameliorates joint inflammation in a murine model of rheumatoid arthritis by modifying collagen-specific T-cell responses and downregulating antigen-presenting cells

In Ah Choi, Ji Yong Choi, Sundo Jung, Fathihah Basri, Se-Ho Park, Eun Young Lee

Research output: Contribution to journalArticle

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Abstract

This study investigated whether GV1001 may be useful for treating rheumatoid arthritis (RA). Two collagen-induced arthritis (CIA) experiments showed that therapeutic, but not preventive, GV1001 treatment reduced the severity of joint inflammation in CIA. The third CIA experiment indicated that, compared to vehicle treatment, therapeutic GV1001 treatment was associated with a significantly smaller area under the curve for the overall clinical joint score over the 98 day observation period (p < 0.05). GV1001 treatment was also associated with lower Day 98 serum IL-6 levels (p < 0.01) and histological joint scores (p < 0.05). Moreover, splenocytes harvested from the GV1001-treated mice exhibited lower basal and collagen-stimulated production of IFN-γ and IL-6 on Days 49 and 98 than the splenocytes from vehicle-treated mice. The fourth and fifth experiments indicated that earlier treatment resulted in a better response. In addition, human (THP-1) and murine (RAW 264.7) macrophages and fibroblast-like synoviocytes (FLS) from RA patients were used for in vitro analyses. GV1001 treatment of lipopolysaccharide-stimulated macrophages derived from THP-1 and RAW 264.7 monocytes significantly reduced TNF-α and IL-6 secretion (THP-1: all p < 0.05; RAW 264.7: all p < 0.01). However, GV1001 treatment did not affect IL-6 expression in TNFα-stimulated RA FLS. GV1001 reduced the clinical joint scores, serum IL-6 levels, and histological joint scores of mice with CIA. In addition, GV1001 lowered the collagen-stimulated IFN-γ and IL-6 production of murine T-cells and reduced the TNF-α and IL-6 production of macrophages in vitro. Thus, GV1001 may ameliorate joint inflammation by modifying T-cell reactions to the triggering autoantigen and by reducing macrophage cytokine production.

Original languageEnglish
Pages (from-to)186-193
Number of pages8
JournalInternational Immunopharmacology
Volume46
DOIs
Publication statusPublished - 2017 May 1

Fingerprint

Antigen-Presenting Cells
Immunotherapy
Rheumatoid Arthritis
Collagen
Down-Regulation
Joints
Inflammation
T-Lymphocytes
Interleukin-6
Experimental Arthritis
Macrophages
Therapeutics
Fibroblasts
Serum
Area Under Curve
Lipopolysaccharides
Monocytes
Observation
Cytokines

Keywords

  • Rheumatoid arthritis
  • T-cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

GV1001 immunotherapy ameliorates joint inflammation in a murine model of rheumatoid arthritis by modifying collagen-specific T-cell responses and downregulating antigen-presenting cells. / Choi, In Ah; Choi, Ji Yong; Jung, Sundo; Basri, Fathihah; Park, Se-Ho; Lee, Eun Young.

In: International Immunopharmacology, Vol. 46, 01.05.2017, p. 186-193.

Research output: Contribution to journalArticle

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abstract = "This study investigated whether GV1001 may be useful for treating rheumatoid arthritis (RA). Two collagen-induced arthritis (CIA) experiments showed that therapeutic, but not preventive, GV1001 treatment reduced the severity of joint inflammation in CIA. The third CIA experiment indicated that, compared to vehicle treatment, therapeutic GV1001 treatment was associated with a significantly smaller area under the curve for the overall clinical joint score over the 98 day observation period (p < 0.05). GV1001 treatment was also associated with lower Day 98 serum IL-6 levels (p < 0.01) and histological joint scores (p < 0.05). Moreover, splenocytes harvested from the GV1001-treated mice exhibited lower basal and collagen-stimulated production of IFN-γ and IL-6 on Days 49 and 98 than the splenocytes from vehicle-treated mice. The fourth and fifth experiments indicated that earlier treatment resulted in a better response. In addition, human (THP-1) and murine (RAW 264.7) macrophages and fibroblast-like synoviocytes (FLS) from RA patients were used for in vitro analyses. GV1001 treatment of lipopolysaccharide-stimulated macrophages derived from THP-1 and RAW 264.7 monocytes significantly reduced TNF-α and IL-6 secretion (THP-1: all p < 0.05; RAW 264.7: all p < 0.01). However, GV1001 treatment did not affect IL-6 expression in TNFα-stimulated RA FLS. GV1001 reduced the clinical joint scores, serum IL-6 levels, and histological joint scores of mice with CIA. In addition, GV1001 lowered the collagen-stimulated IFN-γ and IL-6 production of murine T-cells and reduced the TNF-α and IL-6 production of macrophages in vitro. Thus, GV1001 may ameliorate joint inflammation by modifying T-cell reactions to the triggering autoantigen and by reducing macrophage cytokine production.",
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