Co‐expression of TNFα and IL‐1β in human acute pulmonary fibrotic diseases: An immunohistochemical analysis

Pan, Lingai; Ohtani, Haruo; Yamauchi, Kohei; Nishimura, Hiroshi

doi:10.1111/j.1440-1827.1996.tb03584.x

Cited by 107 publications

(69 citation statements)

References 23 publications

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“…We report in the present study that inhibition of GSK-3p reduces the biosynthesis and/or effects of the pro-inflammatory cytokines TNF-a and IL-l. There is good evidence that TNF-a and IL-l pare involved in the pathogenesis of lung fibrosis; these cytokines are present in lung tissues and can be detected immunohistochemically in the inflamed tissues (26). Direct evidence that TNF-a and IL-l p playa role in the pathogenesis of experimental lung injury has been demonstrated in animal models in which inhibition ofthese cytokines has been shown to delay the onset of experimental lung injury, suppress inflammation, and ameliorate lung destruction that corresponds to the anti-inflammatory response (27).…”

Section: Effects Of Tdzd-8 On Changes In Body Weight and Survival Ratementioning

confidence: 99%

Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury

Cuzzocrea

Genovese

Mazzon

et al. 2007

Int J Immunopathol Pharmacol

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Glycogen synthase kinase-3 (GSK-3) is an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study is to investigate the effects of TDZD-8, a potent and selective GSK-3β inhibitor, on the development of lung injury caused by administration of bleomycin (BLM). Mice subjected to intra-tracheal administration of BLM developed significant lung injury characterized by marked neutrophil infiltration and tissue edema. An increase in immunoreactivity to nitrotyrosine, iNOS, TNF-α and IL-1β was also observed in the lungs of BLM-treated mice. In contrast, administration of BLM-treated mice with TDZD-8 (1 mg/kg daily) significantly reduced (I) the degree of lung injury, (II) the increase in staining (immunohistochemistry) for myeloperoxidase (MPO), nitrotyrosine, iNOS, TNF-α and IL-1β and (III) the degree of apoptosis, as evaluated by Bax and Bcl-2 immunoreactivity and TUNEL staining. Taken together, these results clearly demonstrate treatment with the GSK-3β inhibitor TDZD-8 reduces the development of lung injury and inflammation induced by BLM in mice.

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Section: Effects Of Tdzd-8 On Changes In Body Weight and Survival Ratementioning

confidence: 99%

Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury

Cuzzocrea

Genovese

Mazzon

et al. 2007

Int J Immunopathol Pharmacol

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“…2,27 Under normal conditions, myofibroblasts are transient but essential cells that function in the resolution of inflammation and scar formation; these cells are cleared from the wound site by apoptosis. 28,29 However, in IPF, because of the release of fibrogenic cytokines such as tumor necrosis factor (TNF)-␣, 30,31 interleukin (IL)-1, 31 and basic fibroblast growth factor, 32 these myofibroblasts are differentiated and activated. 3 An in vitro study showed that the primary cultures of fibroblasts from IPF patients contain significantly greater numbers of myofibroblasts than the cultures from patients without pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Discoidin Domain Receptor 1 Contributes to the Survival of Lung Fibroblast in Idiopathic Pulmonary Fibrosis

Matsuyama

Watanabe

Shirahama

et al. 2006

The American Journal of Pathology

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Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast proliferation and accumulation of extracellular matrix, including collagen, is a chronic progressive disorder that results in lung remodeling and fibrosis. However, the cellular mechanisms that may make fibroblasts resistant to apoptosis have not been completely elucidated. Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase whose ligand is collagen, is expressed in vivo and contributes in vitro to leukocyte differentiation and nuclear factor (NF)-B activation, which may play an important role in fibroblast survival. In this study, we examined in vivo and in vitro DDR1 expression and its role in cell survival using fibroblasts obtained from IPF and non-IPF patients. Immunohistochemically, fibroblasts present in fibroblastic foci expressed endogenous DDR1. The DDR1 expression level was significantly higher in fibroblasts from IPF patients, and the predominant isoform was DDR1b. In IPF patients, DDR1 activation in fibroblasts inhibited Fas ligand-induced apoptosis and resulted in NF-B nuclear translocation. Suppression of DDR1 expression in fibroblasts by siRNA abolished these effects, and an NF-B inhibitor abrogated the anti-apoptotic effect of DDR1 activation. We propose that DDR1 contributes to fibroblast survival in the tissue microenvironment of IPF and that DDR1 up-regulation may occur in other fibroproliferative lung diseases as well. (Am J Pathol

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“…Tumour necrosis factor and related genes Expression analysis of TNF-a in lung tissue from patients with IPF has shown elevated levels in (regenerating) type-II pneumocytes [41][42][43]. WHYTE et al [30] first reported an association between the TNF gene and IPF.…”

Section: Pro-/anti-inflammationmentioning

confidence: 99%

Genetics of fibrosing lung diseases

Grutters

Bois²

2005

Eur Respir J

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Genetic studies in familial lung fibrosis have demonstrated an association with surfactant protein C genes: two mutations have been found resulting in protein misfolding and causing type-II epithelial cell injury. Remarkably, different histological patterns were observed in the affected subjects, suggesting the influence of modifier genes and/or environmental factors. Surfactant protein C gene variations have not, however, been associated with sporadic cases,i.e.idiopathic pulmonary fibrosis (IPF).Susceptibility to IPF probably involves a combination of polymorphisms related to epithelial cell injury and abnormal wound healing. To date, the genetic associations with IPF that have been reported in different cohorts include the genes encoding tumour necrosis factor (TNF; −308 adenine), interleukin-1 receptor antagonist (+2018 thymidine) and association with severity and progression (interleukin-6/TNF receptor II and transforming growth factor-β1 (TGFB1; +869 cytosine)), but none of these associations have been replicated by others.Unlike in IPF, immunological inflammation seems to be more prominent in the pathogenesis of scleroderma lung fibrosis, being an autoimmune disease with specific autoantibodies, such as antitopoisomerase antibodies, in patients with diffuse lung disease, and anticentromere antibodies, in patients with pulmonary vascular disease. Antitopoisomerase antibody positivity is associated with the carriage of human leukocyte antigen DRB1*11 and DPB1*1301 alleles, suggesting the recognition of a specific amino-acid motif. Extended haplotype analysis also supports the conclusion that TNF may be the primary association with anticentromere positivity. Intriguingly, associations with TGFB1 and genes involved in extracellular matrix homeostasis have been reported in this disease.In conclusion, significant steps forward have been taken in the understanding of the genetic contribution to fibrosing lung diseases, but major challenges lay ahead. It is the present authors' opinion that only a combined approach studying large numbers of familial and sporadic cases, all clinically well phenotyped, using multiple distinct cohorts, and genotyped according to relevant gene ontologies will be successful. It will be necessary to be particularly vigilant with regard to phenotype; the absence of very strong reproducible associations may be because of the rigidity of phenotype definition, coupled with the possibility that idiopathic pulmonary fibrosis may still be a heterogeneous group of diseases, despite the more rigid definition set out by the European Respiratory Society/American Thoracic Society statement.

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Co‐expression of TNFα and IL‐1β in human acute pulmonary fibrotic diseases: An immunohistochemical analysis

Cited by 107 publications

References 23 publications

Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury

Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury

RETRACTED: Discoidin Domain Receptor 1 Contributes to the Survival of Lung Fibroblast in Idiopathic Pulmonary Fibrosis

Genetics of fibrosing lung diseases

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