Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice.

Nina Kesel; Dorothee Köhler; Lena Herich; Martin Laudien; Konstanze Holl-Ulrich; Astrid Jüngel; Michel Neidhart; Steffen Gay; Renate E Gay; Elena Csernok; Peter Lamprecht; Wolfgang L Gross; Udo Schumacher; Sebastian Ullrich

Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice.

Standard

Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice. / Kesel, Nina; Köhler, Dorothee; Herich, Lena; Laudien, Martin; Holl-Ulrich, Konstanze; Jüngel, Astrid; Neidhart, Michel; Gay, Steffen; Gay, Renate E; Csernok, Elena; Lamprecht, Peter; Gross, Wolfgang L; Schumacher, Udo; Ullrich, Sebastian.

In: AM J PATHOL, Vol. 180, No. 5, 5, 2012, p. 2144-2155.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kesel, N, Köhler, D, Herich, L, Laudien, M, Holl-Ulrich, K, Jüngel, A, Neidhart, M, Gay, S, Gay, RE, Csernok, E, Lamprecht, P, Gross, WL, Schumacher, U & Ullrich, S 2012, 'Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice.', AM J PATHOL, vol. 180, no. 5, 5, pp. 2144-2155. <http://www.ncbi.nlm.nih.gov/pubmed/22449947?dopt=Citation>

APA

Kesel, N., Köhler, D., Herich, L., Laudien, M., Holl-Ulrich, K., Jüngel, A., Neidhart, M., Gay, S., Gay, R. E., Csernok, E., Lamprecht, P., Gross, W. L., Schumacher, U., & Ullrich, S. (2012). Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice. AM J PATHOL, 180(5), 2144-2155. [5]. http://www.ncbi.nlm.nih.gov/pubmed/22449947?dopt=Citation

Vancouver

Kesel N, Köhler D, Herich L, Laudien M, Holl-Ulrich K, Jüngel A et al. Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice. AM J PATHOL. 2012;180(5):2144-2155. 5.

Bibtex

@article{221a85fded4541cda289133926b7eac3,

title = "Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice.",

abstract = "A key feature of granulomatosis with polyangiitis (GPA; or Wegener's granulomatosis) is the granulomatous inflammation of the upper respiratory tract, which leads to the subsequent destruction of adjacent tissues. The aim of our work was to study the histopathological and cellular components of tissue destruction of human GPA tissue transplanted into immunodeficient mice. Biopsy specimens from patients with active GPA (n = 10) or sinusitis (controls, n = 6) were s.c. co-implanted with healthy allogeneic human nasal cartilage into immunodeficient pfp/rag2(-/-) mice. Transplants were examined for their destructive capability of the allografted human cartilage. In addition, nasal fibroblasts from patients with GPA (n = 8) and control healthy nasal fibroblasts (n = 5) were cultured, and cell proliferation and apoptosis were quantified. mRNA and protein levels of matrix metalloproteinases and cytokines were evaluated at baseline and after proinflammatory stimulation. GPA implants showed massive destruction of the co-implanted human cartilage, whereas cartilage destruction was only marginal in control samples. Destruction was mediated by human fibroblasts and could be inhibited by corticoid treatment. The up-regulated production of matrix metalloproteinases 1, 3, and 13 and cytokines IL-6 and IL-8 was found in vivo and in vitro. Although proliferation of isolated fibroblasts was comparable between GPA and controls, GPA samples showed a significant delay of apoptosis. The destruction of nasal cartilage in GPA is mainly mediated by fibroblasts that can be blocked by corticosteroids, and this tissue destruction is not dependent on the influx of leukocytes.",

keywords = "Adult, Animals, Humans, Male, Aged, Female, Middle Aged, Young Adult, Cells, Cultured, Mice, Mice, Knockout, Cell Proliferation, Gene Expression Profiling/methods, Real-Time Polymerase Chain Reaction/methods, RNA, Messenger/genetics, Cytokines/biosynthesis, Apoptosis/physiology, Immune Tolerance, Dexamethasone/pharmacology/therapeutic use, Fibroblasts/drug effects/metabolism/*physiology, Glucocorticoids/pharmacology/therapeutic use, Matrix Metalloproteinases/biosynthesis, Nasal Cartilages/*pathology/transplantation, Nasal Mucosa/pathology/transplantation, Nose Deformities, Acquired/etiology/pathology, Wegener Granulomatosis/complications/drug therapy/*pathology, Adult, Animals, Humans, Male, Aged, Female, Middle Aged, Young Adult, Cells, Cultured, Mice, Mice, Knockout, Cell Proliferation, Gene Expression Profiling/methods, Real-Time Polymerase Chain Reaction/methods, RNA, Messenger/genetics, Cytokines/biosynthesis, Apoptosis/physiology, Immune Tolerance, Dexamethasone/pharmacology/therapeutic use, Fibroblasts/drug effects/metabolism/*physiology, Glucocorticoids/pharmacology/therapeutic use, Matrix Metalloproteinases/biosynthesis, Nasal Cartilages/*pathology/transplantation, Nasal Mucosa/pathology/transplantation, Nose Deformities, Acquired/etiology/pathology, Wegener Granulomatosis/complications/drug therapy/*pathology",

author = "Nina Kesel and Dorothee K{\"o}hler and Lena Herich and Martin Laudien and Konstanze Holl-Ulrich and Astrid J{\"u}ngel and Michel Neidhart and Steffen Gay and Gay, {Renate E} and Elena Csernok and Peter Lamprecht and Gross, {Wolfgang L} and Udo Schumacher and Sebastian Ullrich",

year = "2012",

language = "English",

volume = "180",

pages = "2144--2155",

journal = "AM J PATHOL",

issn = "0002-9440",

publisher = "Elsevier Inc.",

number = "5",

}

RIS

TY - JOUR

T1 - Cartilage destruction in granulomatosis with polyangiitis (Wegener's granulomatosis) is mediated by human fibroblasts after transplantation into immunodeficient mice.

AU - Kesel, Nina

AU - Köhler, Dorothee

AU - Herich, Lena

AU - Laudien, Martin

AU - Holl-Ulrich, Konstanze

AU - Jüngel, Astrid

AU - Neidhart, Michel

AU - Gay, Steffen

AU - Gay, Renate E

AU - Csernok, Elena

AU - Lamprecht, Peter

AU - Gross, Wolfgang L

AU - Schumacher, Udo

AU - Ullrich, Sebastian

PY - 2012

Y1 - 2012

N2 - A key feature of granulomatosis with polyangiitis (GPA; or Wegener's granulomatosis) is the granulomatous inflammation of the upper respiratory tract, which leads to the subsequent destruction of adjacent tissues. The aim of our work was to study the histopathological and cellular components of tissue destruction of human GPA tissue transplanted into immunodeficient mice. Biopsy specimens from patients with active GPA (n = 10) or sinusitis (controls, n = 6) were s.c. co-implanted with healthy allogeneic human nasal cartilage into immunodeficient pfp/rag2(-/-) mice. Transplants were examined for their destructive capability of the allografted human cartilage. In addition, nasal fibroblasts from patients with GPA (n = 8) and control healthy nasal fibroblasts (n = 5) were cultured, and cell proliferation and apoptosis were quantified. mRNA and protein levels of matrix metalloproteinases and cytokines were evaluated at baseline and after proinflammatory stimulation. GPA implants showed massive destruction of the co-implanted human cartilage, whereas cartilage destruction was only marginal in control samples. Destruction was mediated by human fibroblasts and could be inhibited by corticoid treatment. The up-regulated production of matrix metalloproteinases 1, 3, and 13 and cytokines IL-6 and IL-8 was found in vivo and in vitro. Although proliferation of isolated fibroblasts was comparable between GPA and controls, GPA samples showed a significant delay of apoptosis. The destruction of nasal cartilage in GPA is mainly mediated by fibroblasts that can be blocked by corticosteroids, and this tissue destruction is not dependent on the influx of leukocytes.

AB - A key feature of granulomatosis with polyangiitis (GPA; or Wegener's granulomatosis) is the granulomatous inflammation of the upper respiratory tract, which leads to the subsequent destruction of adjacent tissues. The aim of our work was to study the histopathological and cellular components of tissue destruction of human GPA tissue transplanted into immunodeficient mice. Biopsy specimens from patients with active GPA (n = 10) or sinusitis (controls, n = 6) were s.c. co-implanted with healthy allogeneic human nasal cartilage into immunodeficient pfp/rag2(-/-) mice. Transplants were examined for their destructive capability of the allografted human cartilage. In addition, nasal fibroblasts from patients with GPA (n = 8) and control healthy nasal fibroblasts (n = 5) were cultured, and cell proliferation and apoptosis were quantified. mRNA and protein levels of matrix metalloproteinases and cytokines were evaluated at baseline and after proinflammatory stimulation. GPA implants showed massive destruction of the co-implanted human cartilage, whereas cartilage destruction was only marginal in control samples. Destruction was mediated by human fibroblasts and could be inhibited by corticoid treatment. The up-regulated production of matrix metalloproteinases 1, 3, and 13 and cytokines IL-6 and IL-8 was found in vivo and in vitro. Although proliferation of isolated fibroblasts was comparable between GPA and controls, GPA samples showed a significant delay of apoptosis. The destruction of nasal cartilage in GPA is mainly mediated by fibroblasts that can be blocked by corticosteroids, and this tissue destruction is not dependent on the influx of leukocytes.

KW - Adult

KW - Animals

KW - Humans

KW - Male

KW - Aged

KW - Female

KW - Middle Aged

KW - Young Adult

KW - Cells, Cultured

KW - Mice

KW - Mice, Knockout

KW - Cell Proliferation

KW - Gene Expression Profiling/methods

KW - Real-Time Polymerase Chain Reaction/methods

KW - RNA, Messenger/genetics

KW - Cytokines/biosynthesis

KW - Apoptosis/physiology

KW - Immune Tolerance

KW - Dexamethasone/pharmacology/therapeutic use

KW - Fibroblasts/drug effects/metabolism/physiology

KW - Glucocorticoids/pharmacology/therapeutic use

KW - Matrix Metalloproteinases/biosynthesis

KW - Nasal Cartilages/pathology/transplantation

KW - Nasal Mucosa/pathology/transplantation

KW - Nose Deformities, Acquired/etiology/pathology

KW - Wegener Granulomatosis/complications/drug therapy/pathology