FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3

Yohei Ikezumi, Katsue Kanno, Hiroko Koike, Masayuki Tomita, Makoto Uchiyama, Fujio Shimizu, Hiroshi Kawachi

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background. We have previously reported that CD4 T lymphocytes and their cytokines contribute to development of Thy 1.1 glomerulonephritis (GN). FK506 is reported to suppress the production of Th1 cytokines. The aims of this study were to elucidate the role of Th1 cytokines on mesangial alteration and to examine whether FK506 is available for therapy of mesangial proliferative GN. Methods. The effects of daily treatments of FK506 from day -5 and from day +1 of Thy 1.1 GN induction on glomerular alterations were analyzed. Results. FK506 treatment with 1.0 and 0.3 mg/kg body weight (BW) daily from day 1 to day 4 significantly reduced the glomerular expression of mRNA for interferon-γ (IFN-γ 1.0 mg/kg BW FK506, 32.4% to the placebo group, P < 0.01) and IL-2 (55.6%, P < 0.01) on day 5. FK506 treatment from day -5 of GN induction reduced proteinuria and glomerular alteration in a dose-dependent manner. Although no side effects were detected in rats with 0.3 mg/kg BW of FK506 treatment from day +1, the treatment also ameliorated proteinuria (day 14, 3.7 ± 0.89 vs. 19.8 ± 12.3 mg/100 g BW/day P < 0.05) and glomerular alterations [total cell number, 63.1 ± 3.1 vs. 80.2 ± 7.4, P < 0.01; matrix expansion, 0.90 ± 0.30 vs. 1.34 ± 0.27, P < 0.05; α-smooth muscle actin (αSMA) expression; 1.20 ± 0.12 vs. 1.96 ± 0.29, P < 0.01] on day 14. Conclusion. Th1 cytokines may play an important role in the development of mesangial proliferative glomerulonephritis, and could be targets for therapy. FK506 might be available for clinical use.

Original languageEnglish
Pages (from-to)1339-1350
Number of pages12
JournalKidney International
Volume61
Issue number4
DOIs
Publication statusPublished - 01-01-2002

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Tacrolimus
Proteinuria
Monoclonal Antibodies
Glomerulonephritis
Body Weight
Cytokines
Therapeutics
anti-Thy antibody
Interferons
Interleukin-2
Smooth Muscle
Actins
Cell Count
Placebos
T-Lymphocytes
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Ikezumi, Yohei ; Kanno, Katsue ; Koike, Hiroko ; Tomita, Masayuki ; Uchiyama, Makoto ; Shimizu, Fujio ; Kawachi, Hiroshi. / FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3. In: Kidney International. 2002 ; Vol. 61, No. 4. pp. 1339-1350.
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title = "FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3",
abstract = "Background. We have previously reported that CD4 T lymphocytes and their cytokines contribute to development of Thy 1.1 glomerulonephritis (GN). FK506 is reported to suppress the production of Th1 cytokines. The aims of this study were to elucidate the role of Th1 cytokines on mesangial alteration and to examine whether FK506 is available for therapy of mesangial proliferative GN. Methods. The effects of daily treatments of FK506 from day -5 and from day +1 of Thy 1.1 GN induction on glomerular alterations were analyzed. Results. FK506 treatment with 1.0 and 0.3 mg/kg body weight (BW) daily from day 1 to day 4 significantly reduced the glomerular expression of mRNA for interferon-γ (IFN-γ 1.0 mg/kg BW FK506, 32.4{\%} to the placebo group, P < 0.01) and IL-2 (55.6{\%}, P < 0.01) on day 5. FK506 treatment from day -5 of GN induction reduced proteinuria and glomerular alteration in a dose-dependent manner. Although no side effects were detected in rats with 0.3 mg/kg BW of FK506 treatment from day +1, the treatment also ameliorated proteinuria (day 14, 3.7 ± 0.89 vs. 19.8 ± 12.3 mg/100 g BW/day P < 0.05) and glomerular alterations [total cell number, 63.1 ± 3.1 vs. 80.2 ± 7.4, P < 0.01; matrix expansion, 0.90 ± 0.30 vs. 1.34 ± 0.27, P < 0.05; α-smooth muscle actin (αSMA) expression; 1.20 ± 0.12 vs. 1.96 ± 0.29, P < 0.01] on day 14. Conclusion. Th1 cytokines may play an important role in the development of mesangial proliferative glomerulonephritis, and could be targets for therapy. FK506 might be available for clinical use.",
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FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3. / Ikezumi, Yohei; Kanno, Katsue; Koike, Hiroko; Tomita, Masayuki; Uchiyama, Makoto; Shimizu, Fujio; Kawachi, Hiroshi.

In: Kidney International, Vol. 61, No. 4, 01.01.2002, p. 1339-1350.

Research output: Contribution to journalArticle

TY - JOUR

T1 - FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3

AU - Ikezumi, Yohei

AU - Kanno, Katsue

AU - Koike, Hiroko

AU - Tomita, Masayuki

AU - Uchiyama, Makoto

AU - Shimizu, Fujio

AU - Kawachi, Hiroshi

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Background. We have previously reported that CD4 T lymphocytes and their cytokines contribute to development of Thy 1.1 glomerulonephritis (GN). FK506 is reported to suppress the production of Th1 cytokines. The aims of this study were to elucidate the role of Th1 cytokines on mesangial alteration and to examine whether FK506 is available for therapy of mesangial proliferative GN. Methods. The effects of daily treatments of FK506 from day -5 and from day +1 of Thy 1.1 GN induction on glomerular alterations were analyzed. Results. FK506 treatment with 1.0 and 0.3 mg/kg body weight (BW) daily from day 1 to day 4 significantly reduced the glomerular expression of mRNA for interferon-γ (IFN-γ 1.0 mg/kg BW FK506, 32.4% to the placebo group, P < 0.01) and IL-2 (55.6%, P < 0.01) on day 5. FK506 treatment from day -5 of GN induction reduced proteinuria and glomerular alteration in a dose-dependent manner. Although no side effects were detected in rats with 0.3 mg/kg BW of FK506 treatment from day +1, the treatment also ameliorated proteinuria (day 14, 3.7 ± 0.89 vs. 19.8 ± 12.3 mg/100 g BW/day P < 0.05) and glomerular alterations [total cell number, 63.1 ± 3.1 vs. 80.2 ± 7.4, P < 0.01; matrix expansion, 0.90 ± 0.30 vs. 1.34 ± 0.27, P < 0.05; α-smooth muscle actin (αSMA) expression; 1.20 ± 0.12 vs. 1.96 ± 0.29, P < 0.01] on day 14. Conclusion. Th1 cytokines may play an important role in the development of mesangial proliferative glomerulonephritis, and could be targets for therapy. FK506 might be available for clinical use.

AB - Background. We have previously reported that CD4 T lymphocytes and their cytokines contribute to development of Thy 1.1 glomerulonephritis (GN). FK506 is reported to suppress the production of Th1 cytokines. The aims of this study were to elucidate the role of Th1 cytokines on mesangial alteration and to examine whether FK506 is available for therapy of mesangial proliferative GN. Methods. The effects of daily treatments of FK506 from day -5 and from day +1 of Thy 1.1 GN induction on glomerular alterations were analyzed. Results. FK506 treatment with 1.0 and 0.3 mg/kg body weight (BW) daily from day 1 to day 4 significantly reduced the glomerular expression of mRNA for interferon-γ (IFN-γ 1.0 mg/kg BW FK506, 32.4% to the placebo group, P < 0.01) and IL-2 (55.6%, P < 0.01) on day 5. FK506 treatment from day -5 of GN induction reduced proteinuria and glomerular alteration in a dose-dependent manner. Although no side effects were detected in rats with 0.3 mg/kg BW of FK506 treatment from day +1, the treatment also ameliorated proteinuria (day 14, 3.7 ± 0.89 vs. 19.8 ± 12.3 mg/100 g BW/day P < 0.05) and glomerular alterations [total cell number, 63.1 ± 3.1 vs. 80.2 ± 7.4, P < 0.01; matrix expansion, 0.90 ± 0.30 vs. 1.34 ± 0.27, P < 0.05; α-smooth muscle actin (αSMA) expression; 1.20 ± 0.12 vs. 1.96 ± 0.29, P < 0.01] on day 14. Conclusion. Th1 cytokines may play an important role in the development of mesangial proliferative glomerulonephritis, and could be targets for therapy. FK506 might be available for clinical use.

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