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

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

doi:10.1016/j.healun.2010.03.012

Cited by 35 publications

(26 citation statements)

References 57 publications

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“…We and others (8,(12)(13)(14) previously reported that autoimmune responses to col(V) are linked to the pathogenesis of lung fibrosis. We also have previously reported IL-17-dependent anti-col(V) cellular immune responses in patients with OB with lung transplants (as measured by the trans-vivo delayed-type hypersensitivity assay); we attributed this response to be possibly due to the overabundance of induced ␣1(V) chains noted in the OB lesions (14).…”

Section: Il-17 Mediates Specific Rna and Protein Overexpression For Tmentioning

confidence: 83%

IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis

Vittal¹,

Fan²,

Greenspan³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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erative bronchiolitis (OB), a fibrotic airway lesion, is the leading cause of death after lung transplantation. Type V collagen [col(V)] overexpression and IL-17-mediated anti-col(V) immunity are key contributors to OB pathogenesis. Here, we report a previously undefined role of IL-17 in inducing col(V) overexpression, leading to epithelial mesenchymal transition (EMT) and subsequent OB. We observed IL-17-mediated induction of col(V) ␣1 chains [␣1 (V)] in normal airway epithelial cells in vitro and detected ␣1 (V)-specific antibodies in bronchoalveolar lavage fluid of lung transplant patients. Overexpression of IL-17 and col(V) was detected in OB lesions in patient lung biopsies and in a murine OB model. IL-17 is shown to induce EMT, TGF-␤ mRNA expression, and SMAD3 activation, whereas downregulating SMAD7 expression in vitro. Pharmacological inhibition of TGF-␤RI tyrosine kinase, p38 MAPK, or focal adhesion kinase prevented col(V) overexpression and EMT. In murine orthotopic lung transplants, neutralizing IL-17 significantly decreased TGF-␤ mRNA and protein expression and prevented epithelial repair/ OB. Our findings highlight a feed-forward loop between IL-17 and TGF-␤, leading to induction of col(V) and associated epithelial repair, thus providing one possible link between autoimmunity and OB after lung transplantation. autoimmunity; p38 MAPK; focal adhesion kinase; small-airway epithelial cells; RLE-6TN; mouse transplant model; epithelial-mesenchymal transition OBLITERATIVE BRONCHIOLITIS (OB) is characterized by extensive peribronchiolar fibrosis with plugs of granulation tissues (fibroblasts and collagen) that occlude small airways. OB is the key reason that the 5-yr survival of lung transplant recipients is only 50%, the worst of all major solid organ transplants (42,48).Aberrant epithelial repair is a key event in the transplanted lung (1, 9) in which bronchioles lose resident epithelial cells and become occluded by granulation tissue. Abnormal epithelial repair eventually causes an epithelial-to-mesenchymal transition (EMT), a functional and phenotypic change of epithelial cells into spindle-shaped, migratory (43) and matrix-component-secreting mesenchymal cells (10, 41), and a process associated with lung fibrosis (15,27). However, the direct connection between EMT and the in vivo phenomena of fibrosis and fibro-obliterative disease remains controversial.We and others previously reported that OB is associated with dysregulation of two types of collagen: 1) marked increase in type V collagen [col(V)], a quantitatively minor lung collagen (8,14,40), and 2) a decrease in the major lung collagen type I [col(I)] (2, 53). We have shown that prospective monitoring of patients with human lung transplant revealed a critical role of col(V)-specific cellular immunity in OB pathogenesis (14,40). Although overexpression of col(V), an otherwise quantitatively minor collagen, is involved in OB pathology, mechanisms leading to col(V) overexpression are unknown. Thus a mechanistic understanding of the triggers of col(V)...

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Section: Il-17 Mediates Specific Rna and Protein Overexpression For Tmentioning

confidence: 83%

IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis

Vittal¹,

Fan²,

Greenspan³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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show abstract

“…Because IL-17 induces stromal cells and monocytes to produce cytokines and promotes granulopoiesis, it has long been recognized as a possible target for therapy during lung transplantation specifically. Several studies have linked IL-17 to fibrosis in the lung in mouse models of pulmonary fibrosis as well as to idiopathic pulmonary fibrosis in humans (22,24,25). IL-17 may be a key regulator of the airway fibrotic response that drives the development of OB.…”

Section: Potential Mechanism Of Rejection Involving Il-17amentioning

confidence: 99%

Role of Interleukin-17A in Early Graft Rejection After Orthotopic Lung Transplantation in Mice

Chen

2016

Chest

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“…In infection models in mice, there is considerable evidence that IL-17 and/or IL-23 are important in host responses against Klebsiella pneumoniae (Tesmer et al 2008). Furthermore, several studies have now linked IL-17 to fibrosis in the lung in mouse models of pulmonary fibrosis and idiopathic pulmonary fibrosis in humans (Braun et al 2010;Kurasawa et al 2000;Wilson et al 2010 (Figure 2). In this way, identification of distinct IL17 + T cells and even separate subpopulations is relatively simple.…”

Section: Il-17 In Lung Diseasesmentioning

confidence: 99%

“…Wegener granulomatosis (Abdulahad et al 2008), Langerhans histiocytosis (Coury et al 2008), and hypersensitivity pneumonitis (Joshi et al 2009;Simonian et al 2009) have been reported to be linked to IL-17. Pulmonary IL-17 producing γδ T cells have also been detected in response to bleomycin-induced tissue damage, a model for induced pulmonary fibrosis (Braun et al 2010). Conversely, a particular subset of γδ T cells secreting IL-17 has been shown to contribute to hyperinflammatory granulomatous disease and fatal lung tissue damage during pulmonary aspergillosis (Romani et al 2008).…”

Section: Sarcoidosis Pulmonary Fibrosis and Other Interstitial Lung mentioning

confidence: 99%

Lung Diseases - Selected State of the Art Reviews

Irusen¹

2012

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

Cited by 35 publications

References 57 publications

IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis

IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis

Role of Interleukin-17A in Early Graft Rejection After Orthotopic Lung Transplantation in Mice

Lung Diseases - Selected State of the Art Reviews

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