MAP kinase activation and apoptosis in lung tissues from patients with idiopathic pulmonary fibrosis

Yoshida, Koichiro; Kuwano, Kazuyoshi; Hagimoto, Naoki; Watanabe, Kentaro; Matsuba, Tokuji; Fujita, Masaki; Inoshima, Ichiro; Hara, Nobuyuki

doi:10.1002/path.1208

Cited by 137 publications

(112 citation statements)

References 30 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…In addition, monocytederived macrophages secrete MCP-1, IL-8, and MIP-1␣ following DDR1 activation in a p38 MAPK-dependent manner (16). The p38 MAPK is activated in the lung tissue of IPF patients (50), and also in a murine IPF model (51). In addition, the inhibition of p38 MAPK can ameliorate murine bleomycin-induced pulmonary fibrosis (52).…”

Section: Discussionmentioning

confidence: 99%

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Matsuyama

Watanabe

Shirahama

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen. We previously reported the functional expression of DDR1 on human monocyte-derived macrophages in vitro; however, information regarding its role in diseases is limited. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease, and the lesions contain an abundance of collagen. In this study, we examined DDR1 expression on bronchoalveolar lavage fluid (BALF) cells and investigated its functionality using samples obtained from 28 IPF patients, 13 chronic obstructive pulmonary disease patients, and 14 healthy volunteers. The DDR1 expression level in CD14-positive BALF cells was higher in IPF patients than in chronic obstructive pulmonary disease patients or healthy volunteers. The predominant isoform was DDR1b in the IPF group, while DDR1a was predominant in the other two groups. Using immunohistochemical analysis, we also detected DDR1 expression on infiltrating inflammatory cells in the IPF lesion. In IPF patients, DDR1 activation induced the production of MCP-1, IL-8, MIP-1 α, and matrix metalloproteinase-9 (MMP-9) from CD14-positive BALF cells in a p38 MAPK-dependent manner. In contrast, DDR1 activation of CD14-positive BALF cells in the other groups did not induce the production of these chemokines or MMP-9. These chemokines and MMP-9 contribute to the development of IPF and, therefore, we suggest that DDR1 might be associated with the pathogenesis of IPF in the tissue microenvironment.

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Matsuyama

Watanabe

Shirahama

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In the absence of phosphorylated p90RSK, cells arrest and fail to leave the cell cycle [26]. This MAPK pathway is activated by mitogens, growth factors and GPCRs [39]. CCR7 is a GPCR, which requires Gi signalling for proper function.…”

Section: Ccl21 and Pulmonary Fibrosis Em Pierce Et Almentioning

confidence: 99%

Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CC chemokine ligand 21

Pierce¹,

Carpenter²,

Jakubzick³

et al. 2007

Eur Respir J

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is the severest form of idiopathic interstitial pneumonia for which therapeutic targets are needed. Surgical lung biopsy specimens from IPF/UIP patients exhibit focal expression of CC chemokine receptor (CCR) 7, but the identity of these CCR7-positive cells is unknown. The purpose of the present study was to examine the functional and signalling significance of CCR7 expression of primary fibroblasts grown from IPF/UIP and normal surgical lung biopsy specimens.Primary fibroblasts were cultured from surgical lung biopsy specimens from IPF/UIP and normal patients. Fibroblasts treated with or without CC chemokine ligand (CCL) 21 were analysed for functional, transcriptional and proteomic differences using immunocytochemical analysis, gene arrays, Taqman real-time PCR, and migration, proliferation and Western blot assays.CCR7 was expressed by IPF/UIP fibroblasts, but not normal fibroblasts. IPF/UIP fibroblasts, but not normal fibroblasts, showed significant migratory and proliferative responses when exposed to CCL21, which were inhibited by pertussis toxin or neutralising antibodies to CCR7. Exposure of IPF/UIP fibroblasts to CCL21 altered the phosphorylation status of mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2 and ribosomal S6 kinase (90 kDa) in these cells; this was abrogated by pertussis toxin or CCR7-specific small interfering RNA.Together, these data demonstrate that CC chemokine ligand 21 modulates the functional properties of idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblasts, but not normal fibroblasts.

show abstract

“…However, studies of human IPF/UIP tissues demonstrating high rates of apoptosis and increased levels of apoptosis-related markers in AECs generally show relatively little evidence of apoptosis in adjacent fibroblasts/myofibroblasts (20,21,44). Moreover, myofibroblasts in fibroblastic foci of IPF/ UIP have been reported to undergo less apoptotic activity in comparison to myofibroblasts in the fibromyxoid lesions of bronchiolitis obliterans organizing pneumonia (BOOP) (45).…”

Section: Survival (Apoptosis Resistance) Of Myofibroblasts In Ipf Whamentioning

confidence: 99%

Evolving Concepts of Apoptosis in Idiopathic Pulmonary Fibrosis

Thannickal

Horowitz

2006

Proceedings of the American Thoracic Society

324

272

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a chronic, relentlessly progressive fibrosing disease of the lung of unknown etiology. Significant progress has been made in recent years in elucidating key aspects of the pathobiology of IPF. Insights into disease pathogenesis have come from studies of cell biology, growth factor/cytokine signaling, animal models of pulmonary fibrosis, and human IPF cells and tissue. A consistent finding in the ultrastructural pathology of IPF is alveolar epithelial cell injury and apoptosis. Another consistent finding in the histopathology of human IPF, described as usual interstitial pneumonia, is the accumulation of aggregates of myofibroblasts in fibroblastic foci. The extent or profusion of fibroblastic foci in lung biopsies is strongly correlated with increased mortality in patients with IPF. There is emerging evidence that myofibroblasts in IPF/usual interstitial pneumonia, both in the in vivo microenvironment and during the process of differentiation in vitro, acquire resistance to apoptosis. Here, we review the current evidence and mechanisms for this apparent "apoptosis paradox" in the pathogenesis of IPF.

show abstract

MAP kinase activation and apoptosis in lung tissues from patients with idiopathic pulmonary fibrosis

Cited by 137 publications

References 30 publications

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CC chemokine ligand 21

Evolving Concepts of Apoptosis in Idiopathic Pulmonary Fibrosis

Contact Info

Product

Resources

About