Transforming growth factor–β1 gene transfer ameliorates acute lung allograft rejection

Mora, Bassem N.; Boasquevisque, Carlos Henrique Ribeiro; Boglione, Mariano; Ritter, John; Scheule, Ronald K.; Yew, Nelson S.; DeBruyne, Lisa A.; Qin, Lihui; Bromberg, Jonathan S.; Patterson, G. Alexander

doi:10.1016/s0022-5223(00)70086-9

Cited by 19 publications

(15 citation statements)

References 27 publications

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“…This could be attributed to the immunosuppressive effect of n-3 PUFA. TGF-β1 is known as an anti-inflammatory cytokine [36,37]. Previous studies have shown that low plasma n-3 PUFA level is associated with high TGF-β expression in a normal population [36].…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Jian

Zhang

et al. 2008

The Journal of Nutritional Biochemistry

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Section: Discussionmentioning

confidence: 99%

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Jian

Zhang

et al. 2008

The Journal of Nutritional Biochemistry

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“…This leads to the possibility that administration of a TGF-␤-inhibitory agent such as pirfenidone could potentially cause more acute rejection. 25,26 To address this issue, we delayed giving pirfenidone until Days 9 and 16 in some of our experimental animals. At this point, the acute cellular response would have begun, but the development of granulation tissue would be none to minimal.…”

Section: Discussionmentioning

confidence: 99%

“…The results suggest that pirfenidone may be worthy of further evaluation for its effectiveness in preventing or ameliorating OB in lung transplant recipients. Pirfenidone's mechanism of action probably involves TGF-␤; however, pirfenidone is known to interfere with other mediators of fibrosis [23][24][25][26][27][28][29][30][31][32][33][34] and thus additional investigations of its effects on these and other mediators of rejection are necessary.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone Inhibits Obliterative Airway Disease in Mouse Tracheal Allografts

Zhou

Latham

Zander

et al. 2005

The Journal of Heart and Lung Transplantation

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“…lung transplantation. 5,6 Moreover, tolerance has been induced in an orthotopic lung transplant model in association with elevated serum levels of TGF-␤, although alloimmune responses were restored with the administration of neutralizing antibodies to TGF-␤. 7 Despite its potent anti-inflammatory properties that would otherwise seem desirable in transplantation, TGF-␤ has been implicated in the pathogenesis of allograft rejection, and is markedly overexpressed in patients with chronic liver, kidney, and heart rejection.…”

mentioning

confidence: 99%

Smad3 Deficiency Ameliorates Experimental Obliterative Bronchiolitis in a Heterotopic Tracheal Transplantation Model

Ramirez

Takagawa

Sekosan

et al. 2004

The American Journal of Pathology

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Chronic allograft rejection manifested as obliterative bronchiolitis (OB) remains the single greatest impediment to long-term survival after lung transplantation. Transforming growth factor-␤1 (TGF-␤1) has been implicated in the tissue remodeling response associated with OB. Therefore, its intracellular signal transducer, Smad3, is a prime target of investigation. Herein, we examine the role of TGF-␤1, through Smad3, in the development of OB using heterotopic tracheal transplantation in wild-type and Smad3-null mice. TGF-␤1 was detectable within infiltrating mononuclear cells early after transplantation. Throughout the last 20 years, lung transplantation has evolved into an accepted treatment option for patients with end-stage lung disease because of emphysema, pulmonary fibrosis, pulmonary hypertension, and cystic fibrosis. 1 However, chronic allograft rejection manifested as obliterative bronchiolitis (OB) remains the major obstacle to long-term survival after lung transplantation. 2 Clinically, OB is characterized by airflow limitation, defined by a 20% decline in forced expiratory volume in 1 second (FEV 1 ), and is often complicated by recurrent lower respiratory tract infections. The histological hallmark of OB is the presence of obstructing intraluminal polyps comprised of fibromyxoid granulation tissue and plaques of dense submucosal eosinophilic scar on lung biopsy. OB can complicate up to 60% of lung allografts and becomes increasingly prevalent the further removed from the transplant operation. 3 Progressive OB ultimately results in worsening hypoxemia and death.Many studies on the pathogenesis of OB have concentrated on the role of cellular allogenic immune responses during OB development. However, fibroproliferation and tissue remodeling clearly play an important role in its pathogenesis because OB is characterized by the accumulation of fibroblasts and the excessive deposition of connective tissue matrix within the lumen of the affected bronchioles. The factors that initiate and maintain fibroproliferation and tissue remodeling within the airway lumen in OB have not been fully elucidated. One candidate factor is transforming growth factor (TGF)-␤, a pleiotropic cytokine with potent profibrotic activities. 4 Extensively studied in solid organ transplantation, TGF-␤ has been found to have beneficial effects on alloimmunity. For instance, overexpression of a TGF-␤ transgene leads to marked reductions in acute rejection and prolongation of graft survival in experimental heart and

show abstract

Transforming growth factor–β1 gene transfer ameliorates acute lung allograft rejection

Cited by 19 publications

References 27 publications

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Pirfenidone Inhibits Obliterative Airway Disease in Mouse Tracheal Allografts

Smad3 Deficiency Ameliorates Experimental Obliterative Bronchiolitis in a Heterotopic Tracheal Transplantation Model

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