American journal of respiratory cell and molecular biology
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Am. J. Respir. Cell Mol. Biol. · Nov 1997
Interleukin-4 alters epithelial cell differentiation and surfactant homeostasis in the postnatal mouse lung.
Interleukin-4 (IL-4) is a pleotrophic cytokine which is increased during lung injury and inflammation. Epithelial cell morphology and surfactant homeostasis were assessed in 4-52-wk-old transgenic mice in which IL-4 was expressed in the bronchial and bronchiolar epithelial cells under the control of the Clara cell secretory protein promoter (CCSP-IL-4 mice). IL-4 caused progressive pulmonary infiltration with macrophages, lymphocytes, neutrophils, and eosinophils. ⋯ Lung-specific increase in T-cell proliferative responses to mitogenic stimulation and antibody secretion were detected in CCSP-IL-4 mice. Differentiated characteristics of respiratory epithelial cells were dramatically influenced by the chronic production of IL-4 in the conducting airways. Alterations in lung morphology in the CCSP-IL-4 mice are similar to some of those induced by antigenic stimulation or associated with chronic airway inflammation.
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Am. J. Respir. Cell Mol. Biol. · Sep 1997
Allergen-induced cytokine production in atopic disease and its relationship to disease severity.
The Th2 cytokines, interleukin (IL)-4 and IL-5, have an important role in atopic disease. CD30 is a transmembrane molecule that may be expressed on a proportion of activated T-lymphocytes and has been reported to be a marker for Th2 phenotype. Our objective was to compare the in vitro cytokine responses and CD30 expression of peripheral blood mononuclear cells (PBMCs) to stimulation with house dust mite antigen (Dermatophagoides pteronyssinus) in atopic asthmatics, atopic nonasthmatics, and normal subjects, and to see if atopic asthmatic cytokine production correlated with symptomatic disease activity and whether cytokine production was allergen-specific. ⋯ PHA produced minimal levels of IL-4 compared to specific allergen stimulation. It is concluded that different groups of atopic patients exhibit different patterns of allergen-induced cytokine production. In vitro allergen-induced cytokine production in atopic asthmatics correlated with symptomatic disease activity, and is allergen-specific.
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Am. J. Respir. Cell Mol. Biol. · Feb 1997
Pulmonary lymphoid cell activation and cytokine expression in murine AIDS-associated interstitial pneumonitis.
Limited information is available about the pathogenesis of acquired immune deficiency syndrome (AIDS)-associated idiopathic interstitial pneumonitis, a common noninfectious complication of human immunodeficiency virus (HIV) infection. Infection of C57B1/6 mice with LP-BM5 retrovirus, a murine model of AIDS, leads to development of a diffuse interstitial pneumonitis that displays many features of human AIDS-associated interstitial pneumonitis. To further characterize the cellular and molecular features of this lung disease, the temporal development of cellular infiltration, cytokine expression, and virus replication were evaluated in lung tissue of virus-infected mice. ⋯ Similarly, expression by interstitial lung lymphoid cells of mRNA for the proinflammatory cytokine IL-1 and the fibrogenic cytokine transforming growth factor-beta (TGF-beta) was also increased following infection. These results indicate that retrovirus-induced immunodeficiency in mice is associated with infiltration and chronic activation of lymphoid cells in the lungs. Furthermore, simultaneous expression of IL-10, IFN-gamma, and TGF-beta suggests that cytokine-expressing cells in infected lungs may be unresponsive to inhibitory and antiinflammatory effects of IL-10 and/or TGF-beta, thus contributing to chronicity of inflammation in this disorder.
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Am. J. Respir. Cell Mol. Biol. · Jan 1997
Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice.
The incidence of apoptosis and the expression of Fas antigen (Fas)/Fas ligand (FasL) mRNA in bleomycin-induced pulmonary fibrosis in mice were examined. Male ICR mice were intratracheally instilled with bleomycin (5 U/kg of body weight). The controls were injected with sterile saline. ⋯ FasL mRNA was also upregulated in infiltrating lymphocytes after bleomycin treatment, but not in the control mice. The administration of corticosteroids suppressed the expression of Fas and FasL mRNA as well as apoptosis and fibrosis. Although these results do not show that apoptosis mediated by the Fas/FasL system is directly linked to bleomycin-induced fibrosis, we speculate that excessive apoptosis and the Fas/FasL system play a role in the pathogenesis of bleomycin-induced lung injury.
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Am. J. Respir. Cell Mol. Biol. · Jul 1996
In vivo expression of intercellular adhesion molecule 1 in type II pneumocytes during hyperoxia.
Cell-to-cell communication is often disrupted when tissue damage occurs, triggering new signals to cope with the injury. The expression of intercellular adhesion molecule (ICAM-1), a protein involved in the migration, binding, and activation of leukocytes, is markedly increased in mouse lungs damaged by acute hyperoxic exposure. Type I alveolar epithelial cells are sensitive to hyperoxic lung injury, and must be removed from the air spaces following their destruction. ⋯ In the lungs of unexposed animals, ICAM-1 mRNA was detected in many cells-including type I pneumocytes-but not in type II cells. After hyperoxia, ICAM-1 transcripts were detected in bona fide, surfactant protein C mRNA-containing, type II alveolar epithelial cells. This observation suggests that type II cells play an important and previously unrecognized role in pulmonary inflammation from O2 toxicity and emphasizes the importance of type II pneumocytes in alveolar repair after injury.