Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases

Kuwano, Kazuyoshi; Maeyama, Takashige; Inoshima, Ichiro; Ninomiya, Kiyoshi; Hagimoto, Naoki; Yoshimi, Michihiro; Fujita, Masaki; Nakamura, Norio; Shirakawa, Kamon; Hara, Nobuyuki

doi:10.1046/j.1440-1843.2002.00369.x

Cited by 48 publications

(37 citation statements)

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“…The death receptor Fas was found to be expressed in AECs within the lungs of IPF patients and circulating levels of its ligand FasL correlated with disease activity. [40][41][42] Similar observations were observed in animal models. 43,44 Activation of Fas-induced apoptosis of bronchial and AECs is sufficient to initiate a fibrotic response in animal models.…”

supporting

confidence: 70%

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

Uhal

Abdul-Hafez

2008

J Perinatol

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Meconium aspiration injures a number of cell types in the lung, most notably airway and alveolar epithelial lining cells. Recent data show that at least some of the cell death induced by meconium occurs by apoptosis, and therefore has the potential for pharmacologic inhibition through the use of apoptosis blockers or other strategies. Related work in adult animal models of lung injury has shown that apoptosis of lung epithelial cells induces a local (that is, entirely lung tissue specific) renin-angiotensin system (RAS L ). Furthermore, this inducible RAS L is required for the apoptotic response and affects other adjacent cell types through the release of angiotensin II and related peptides. This manuscript reviews the published data supporting this viewpoint as well as more recent works that suggest the involvement of a RAS L in the perinatal lung damage associated with meconium aspiration syndrome (MAS). The implications of these findings regarding their potential for the clinical management of MAS are also discussed.

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supporting

confidence: 70%

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

Uhal

Abdul-Hafez

2008

J Perinatol

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“…TGF-b 1 is believed to play an important role in this dysregulation because it is expressed in an exaggerated fashion in IPF where, in contrast to controls, a sizable percentage of this cytokine is biologically active (45)(46)(47). In fact, the apposition of apoptosis, fibrosis, and the exaggerated expression of TGF-b 1 are well documented in IPF (48)(49)(50)(51). TGF-b 1 is also a critical mediator of the pulmonary fibrosis that is seen after bleomycin administration, a commonly used animal model of IPF (5,52).…”

Section: Discussionmentioning

confidence: 99%

P21 Regulates TGF-β₁–Induced Pulmonary Responses via a TNF-α–Signaling Pathway

Yamasaki¹,

Kang²,

Homer³

et al. 2008

Am J Respir Cell Mol Biol

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Transforming growth factor (TGF)-b 1 is an essential regulatory cytokine that has been implicated in the pathogenesis of diverse facets of the injury and repair responses in the lung. The types of responses that it elicits can be appreciated in studies from our laboratory that demonstrated that the transgenic (Tg) overexpression of TGF-b 1 in the murine lung causes epithelial apoptosis followed by fibrosis, inflammation, and parenchymal destruction. Because a cyclin-dependent kinase inhibitor, p21, is a key regulator of apoptosis, we hypothesized that p21 plays an important role in the pathogenesis of TGF-b 1 -induced tissue responses. To test this hypothesis we evaluated the effect of TGF-b 1 on the expression of p21 in the murine lung. We also characterized the effects of transgenic TGFb 1 in mice with wild-type and null mutant p21 loci. These studies demonstrate that TGF-b 1 is a potent stimulator of p21 expression in the epithelial cells and macrophages in the murine lung. They also demonstrate that TGF-b 1 -induced lung inflammation, fibrosis, myofibroblast accumulation, and alveolar destruction are augmented in the absence of p21, and that these alterations are associated with exaggerated levels of apoptosis and caspase-3 activation. Finally, our studies further demonstrated that TGF-b 1 induces p21 via a TNF-asignaling pathway and that p21 is a negative modulator of TGF-b 1 -induced TNF-a expression. Collectively, our studies demonstrate that p21 regulates TGF-b 1 -induced apoptosis, inflammation, fibrosis, and alveolar remodeling by interacting with TNF-a-signaling pathways.

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“…with a NSIP. Kuwano et al reported increased KL-6 levels in IPF patients with signs of disease progression in the previous three months, compared to stable IPF patients [32]. Again, as this study was performed prior to 2002, one should bear in mind that the diagnosis of IPF was since then reclassified [1].…”

Section: Kl-6mentioning

confidence: 99%

Serum biomarkers in idiopathic pulmonary fibrosis

Blink

Wijsenbeek

Hoogsteden

2010

Pulmonary Pharmacology & Therapeutics

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Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases

Abstract: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.

Cited by 48 publications

References 28 publications

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

P21 Regulates TGF-β₁–Induced Pulmonary Responses via a TNF-α–Signaling Pathway

Serum biomarkers in idiopathic pulmonary fibrosis

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Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases

Abstract: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.

Cited by 48 publications

References 28 publications

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

P21 Regulates TGF-β1–Induced Pulmonary Responses via a TNF-α–Signaling Pathway

Serum biomarkers in idiopathic pulmonary fibrosis

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Product

Resources

About

P21 Regulates TGF-β₁–Induced Pulmonary Responses via a TNF-α–Signaling Pathway