Selective inhibition of collagen gene expression in fibroblasts by an interferon-γ transgene

H. Ari Jaffe; Zhancheng Gao; Yasuji Mori; Liye Li; John Varga

doi:10.1080/019021499270268

Selective inhibition of collagen gene expression in fibroblasts by an interferon-γ transgene

H. Ari Jaffe^*, Zhancheng Gao, Yasuji Mori, Liye Li, John Varga

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Because interferon-gamma (IFN-γ) selectively inhibits collagen gene expression, we hypothesized that expression of IFN-γ cDNA in fibroblasts might be a useful strategy to inhibit the development of fibrosis. A replication-deficient E1^-, E3^- adenovirus vector encoding murine IFN-γ (AdCM VmIFNγ) was constructed. Infection of murine fibroblasts with AdCM VmIFNα in vitro was well tolerated. The results showed that IN F-γ mRNA was expressed in infected cells, and as much as 17.7 ng of mIFN-γ/10⁶ cells was secreted into culture supernatants. Steady-state levels of α1(I) procollagen mRNA were decreased by 90% in infected cells compared to uninfected cells. The inhibition of collagen mRNA expression was partially abrogated with a neutralizing anti-mIFN-γ antibody. Secretion of total collagen by AdCM VmIFVγ-infected fibroblasts was decreased by 60% compared to uninfected cells. Induction cells. Induction of cytokine responsive gene-2 expression in AdCM VmIFNγ-infected cells demonstrated that suppression of collagen production was a selective response. The results suggest a novel strategy of cytokine gene transfer and expression for the treatment of fibrotic lung diseases.

Original language	English (US)
Pages (from-to)	199-215
Number of pages	17
Journal	Experimental Lung Research
Volume	25
Issue number	3
DOIs	https://doi.org/10.1080/019021499270268
State	Published - 1999

Funding

Received 14 July 1997 ; accepted 22 July 198. 9 Supported by the United Scleroderma Federation and the National Institutes of Health ( AR-4392) .0 TheauthorsthankDavidOlsen(CeltrixPharmaceutical,CA)forthegiftofTGF-b ;PaulChristner ( Je€ erson Medical Cllegeo, Phladeilphia) for murine lung Ž broblasts ; and Anne Griffin and Dorothy Sojka for excellent technical assistance. Presented at the 1979American Thoracic Scietoy Meetings, San Francisco, California, USA. Address correspondence to H. Ari Ja€ e, MD, RCCM, Departmet ofnMedicine M/C 74, U3niversity of Illinois at Chicago Cllegeoof Medicine, 840 SuthoWood St., Chicago, IL 6006717, 7U-SA3.

Keywords

Adenovirus
Collagen
Fibroblast
Fibrosis
Interferon-γ
Transgene

ASJC Scopus subject areas

Molecular Biology
Pulmonary and Respiratory Medicine
Clinical Biochemistry

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10.1080/019021499270268

Cite this

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title = "Selective inhibition of collagen gene expression in fibroblasts by an interferon-γ transgene",

abstract = "Because interferon-gamma (IFN-γ) selectively inhibits collagen gene expression, we hypothesized that expression of IFN-γ cDNA in fibroblasts might be a useful strategy to inhibit the development of fibrosis. A replication-deficient E1-, E3- adenovirus vector encoding murine IFN-γ (AdCM VmIFNγ) was constructed. Infection of murine fibroblasts with AdCM VmIFNα in vitro was well tolerated. The results showed that IN F-γ mRNA was expressed in infected cells, and as much as 17.7 ng of mIFN-γ/106 cells was secreted into culture supernatants. Steady-state levels of α1(I) procollagen mRNA were decreased by 90% in infected cells compared to uninfected cells. The inhibition of collagen mRNA expression was partially abrogated with a neutralizing anti-mIFN-γ antibody. Secretion of total collagen by AdCM VmIFVγ-infected fibroblasts was decreased by 60% compared to uninfected cells. Induction cells. Induction of cytokine responsive gene-2 expression in AdCM VmIFNγ-infected cells demonstrated that suppression of collagen production was a selective response. The results suggest a novel strategy of cytokine gene transfer and expression for the treatment of fibrotic lung diseases.",

keywords = "Adenovirus, Collagen, Fibroblast, Fibrosis, Interferon-γ, Transgene",

author = "Jaffe, {H. Ari} and Zhancheng Gao and Yasuji Mori and Liye Li and John Varga",

note = "Funding Information: Received 14 July 1997 ; accepted 22 July 198. 9 Supported by the United Scleroderma Federation and the National Institutes of Health ( AR-4392) .0 TheauthorsthankDavidOlsen(CeltrixPharmaceutical,CA)forthegiftofTGF-b ;PaulChristner ( Je€ erson Medical Cllegeo, Phladeilphia) for murine lung {\v Z} broblasts ; and Anne Griffin and Dorothy Sojka for excellent technical assistance. Presented at the 1979American Thoracic Scietoy Meetings, San Francisco, California, USA. Address correspondence to H. Ari Ja€ e, MD, RCCM, Departmet ofnMedicine M/C 74, U3niversity of Illinois at Chicago Cllegeoof Medicine, 840 SuthoWood St., Chicago, IL 6006717, 7U-SA3.",

year = "1999",

doi = "10.1080/019021499270268",

language = "English (US)",

volume = "25",

pages = "199--215",

journal = "Experimental Lung Research",

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T1 - Selective inhibition of collagen gene expression in fibroblasts by an interferon-γ transgene

AU - Jaffe, H. Ari

AU - Gao, Zhancheng

AU - Mori, Yasuji

AU - Li, Liye

AU - Varga, John

N1 - Funding Information: Received 14 July 1997 ; accepted 22 July 198. 9 Supported by the United Scleroderma Federation and the National Institutes of Health ( AR-4392) .0 TheauthorsthankDavidOlsen(CeltrixPharmaceutical,CA)forthegiftofTGF-b ;PaulChristner ( Je€ erson Medical Cllegeo, Phladeilphia) for murine lung Ž broblasts ; and Anne Griffin and Dorothy Sojka for excellent technical assistance. Presented at the 1979American Thoracic Scietoy Meetings, San Francisco, California, USA. Address correspondence to H. Ari Ja€ e, MD, RCCM, Departmet ofnMedicine M/C 74, U3niversity of Illinois at Chicago Cllegeoof Medicine, 840 SuthoWood St., Chicago, IL 6006717, 7U-SA3.

PY - 1999

Y1 - 1999

N2 - Because interferon-gamma (IFN-γ) selectively inhibits collagen gene expression, we hypothesized that expression of IFN-γ cDNA in fibroblasts might be a useful strategy to inhibit the development of fibrosis. A replication-deficient E1-, E3- adenovirus vector encoding murine IFN-γ (AdCM VmIFNγ) was constructed. Infection of murine fibroblasts with AdCM VmIFNα in vitro was well tolerated. The results showed that IN F-γ mRNA was expressed in infected cells, and as much as 17.7 ng of mIFN-γ/106 cells was secreted into culture supernatants. Steady-state levels of α1(I) procollagen mRNA were decreased by 90% in infected cells compared to uninfected cells. The inhibition of collagen mRNA expression was partially abrogated with a neutralizing anti-mIFN-γ antibody. Secretion of total collagen by AdCM VmIFVγ-infected fibroblasts was decreased by 60% compared to uninfected cells. Induction cells. Induction of cytokine responsive gene-2 expression in AdCM VmIFNγ-infected cells demonstrated that suppression of collagen production was a selective response. The results suggest a novel strategy of cytokine gene transfer and expression for the treatment of fibrotic lung diseases.

AB - Because interferon-gamma (IFN-γ) selectively inhibits collagen gene expression, we hypothesized that expression of IFN-γ cDNA in fibroblasts might be a useful strategy to inhibit the development of fibrosis. A replication-deficient E1-, E3- adenovirus vector encoding murine IFN-γ (AdCM VmIFNγ) was constructed. Infection of murine fibroblasts with AdCM VmIFNα in vitro was well tolerated. The results showed that IN F-γ mRNA was expressed in infected cells, and as much as 17.7 ng of mIFN-γ/106 cells was secreted into culture supernatants. Steady-state levels of α1(I) procollagen mRNA were decreased by 90% in infected cells compared to uninfected cells. The inhibition of collagen mRNA expression was partially abrogated with a neutralizing anti-mIFN-γ antibody. Secretion of total collagen by AdCM VmIFVγ-infected fibroblasts was decreased by 60% compared to uninfected cells. Induction cells. Induction of cytokine responsive gene-2 expression in AdCM VmIFNγ-infected cells demonstrated that suppression of collagen production was a selective response. The results suggest a novel strategy of cytokine gene transfer and expression for the treatment of fibrotic lung diseases.

KW - Adenovirus

KW - Collagen

KW - Fibroblast

KW - Fibrosis

KW - Interferon-γ

KW - Transgene

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DO - 10.1080/019021499270268

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AN - SCOPUS:0032901003

SN - 0190-2148

VL - 25

SP - 199

EP - 215

JO - Experimental Lung Research

JF - Experimental Lung Research

IS - 3

ER -

Selective inhibition of collagen gene expression in fibroblasts by an interferon-γ transgene

Abstract

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Keywords

ASJC Scopus subject areas

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