Inhibition of bleomycin-induced pulmonary fibrosis through pre-treatment with collagen type v

Ruedi K. Braun, Alicia Martin, Shivanee Shah, Makio Iwashima, Melissa Medina, Kathryn Byrne, Periannan Sethupathi, Christopher H. Wigfield, David Brand, Robert B. Love

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Tolerance to collagen structures has been shown to inhibit the progression of autoimmune scleroderma and rheumatoid arthritis. More recently, tolerance induction to collagen type V (colV) in experimental models of lung transplantation was shown to ameliorate the complex pathology known as "chronic rejection." The link between colV autoimmunity and progressive graft dysfunction and subsequent development of bronchiolitis obliterans syndrome (BOS) has been established in human lung transplant recipients. We hypothesized that intravenous injection of colV inhibits development of lung fibrosis in a bleomycin-induced lung injury mouse model. Methods: Experimental animals were injected intravenously with saline or colV 10 days before intratracheal instillation of bleomycin. Pulmonary inflammation was monitored and quantified for the presence of cells in the bronchoalveolar lavage (BAL) fluid by flow cytometry and histology of lung tissue. Results: ColVpre-treated animals showed a significant reduction in lung inflammation compared with non-treated animals, according to histology and morphometry. The number of inflammatory cells in the BAL fluid was significantly reduced and associated with a lower proportion of γδ T cells and CD4+ T cells in the colVpre-treated group. Matrix metalloproteinase-2 and -9 (MMP-2 and -9; also known as gelatinase A and gelatinase B, respectively) levels in the BAL fluid were significantly reduced in colVpre-treated mice compared with the non-treated mice. In addition, intravenous injection of colV was associated with a significant reduction in the relative expression of interleukin (IL)-6, IL-17 and IL-22 in cells present in BAL fluid at 7 and 14 days after bleomycin instillation. Conclusions: Pre-treatment by intravenous injection of colV inhibits bleomycin-induced pulmonary fibrosis by inhibiting IL-6 and IL-17 production. Fibrosis treatment in this context therefore should target induction of colV tolerance and Th17 development.

Original languageEnglish (US)
Pages (from-to)873-880
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume29
Issue number8
DOIs
StatePublished - May 14 2010
Externally publishedYes

Fingerprint

Collagen Type V
Pulmonary Fibrosis
Bleomycin
Collagen
Bronchoalveolar Lavage Fluid
Intravenous Injections
Interleukin-17
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Lung
Interleukin-6
Pneumonia
Histology
Fibrosis
Therapeutics
Collagen Type X
Bronchiolitis Obliterans
T-Lymphocytes
Lung Transplantation
Lung Injury

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Inhibition of bleomycin-induced pulmonary fibrosis through pre-treatment with collagen type v. / Braun, Ruedi K.; Martin, Alicia; Shah, Shivanee; Iwashima, Makio; Medina, Melissa; Byrne, Kathryn; Sethupathi, Periannan; Wigfield, Christopher H.; Brand, David; Love, Robert B.

In: Journal of Heart and Lung Transplantation, Vol. 29, No. 8, 14.05.2010, p. 873-880.

Research output: Contribution to journalArticle

Braun, RK, Martin, A, Shah, S, Iwashima, M, Medina, M, Byrne, K, Sethupathi, P, Wigfield, CH, Brand, D & Love, RB 2010, 'Inhibition of bleomycin-induced pulmonary fibrosis through pre-treatment with collagen type v', Journal of Heart and Lung Transplantation, vol. 29, no. 8, pp. 873-880. https://doi.org/10.1016/j.healun.2010.03.012
Braun, Ruedi K. ; Martin, Alicia ; Shah, Shivanee ; Iwashima, Makio ; Medina, Melissa ; Byrne, Kathryn ; Sethupathi, Periannan ; Wigfield, Christopher H. ; Brand, David ; Love, Robert B. / Inhibition of bleomycin-induced pulmonary fibrosis through pre-treatment with collagen type v. In: Journal of Heart and Lung Transplantation. 2010 ; Vol. 29, No. 8. pp. 873-880.
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abstract = "Background: Tolerance to collagen structures has been shown to inhibit the progression of autoimmune scleroderma and rheumatoid arthritis. More recently, tolerance induction to collagen type V (colV) in experimental models of lung transplantation was shown to ameliorate the complex pathology known as {"}chronic rejection.{"} The link between colV autoimmunity and progressive graft dysfunction and subsequent development of bronchiolitis obliterans syndrome (BOS) has been established in human lung transplant recipients. We hypothesized that intravenous injection of colV inhibits development of lung fibrosis in a bleomycin-induced lung injury mouse model. Methods: Experimental animals were injected intravenously with saline or colV 10 days before intratracheal instillation of bleomycin. Pulmonary inflammation was monitored and quantified for the presence of cells in the bronchoalveolar lavage (BAL) fluid by flow cytometry and histology of lung tissue. Results: ColVpre-treated animals showed a significant reduction in lung inflammation compared with non-treated animals, according to histology and morphometry. The number of inflammatory cells in the BAL fluid was significantly reduced and associated with a lower proportion of γδ T cells and CD4+ T cells in the colVpre-treated group. Matrix metalloproteinase-2 and -9 (MMP-2 and -9; also known as gelatinase A and gelatinase B, respectively) levels in the BAL fluid were significantly reduced in colVpre-treated mice compared with the non-treated mice. In addition, intravenous injection of colV was associated with a significant reduction in the relative expression of interleukin (IL)-6, IL-17 and IL-22 in cells present in BAL fluid at 7 and 14 days after bleomycin instillation. Conclusions: Pre-treatment by intravenous injection of colV inhibits bleomycin-induced pulmonary fibrosis by inhibiting IL-6 and IL-17 production. Fibrosis treatment in this context therefore should target induction of colV tolerance and Th17 development.",
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AU - Braun, Ruedi K.

AU - Martin, Alicia

AU - Shah, Shivanee

AU - Iwashima, Makio

AU - Medina, Melissa

AU - Byrne, Kathryn

AU - Sethupathi, Periannan

AU - Wigfield, Christopher H.

AU - Brand, David

AU - Love, Robert B.

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