Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthesis of heat shock proteins (HSPs) is induced in all cells and tissues after exposure to elevated temperatures, or a variety of other types of injury, including oxidative injury. We have previously reported that stress proteins are induced in monocytes-macrophages during phagocytosis of red blood cells. Receptor-mediated phagocytosis is associated with activation of the respiratory burst, generation of the lipid mediators of inflammation, and increased production of cytokines. Similar activation events have been described in the alveolar macrophage (AM) during pulmonary fibrosis. We therefore analysed the pattern of proteins synthesized by human AMs recovered by bronchoalveolar lavage (BAL) in interstitial lung disease, both under basal conditions and after in vitro exposure to heat or hydrogen peroxide (H2O2). In two out of the 17 cases studied, we observed a high alveolar eosinophilia (10 and 24%, respectively) and phagocytosis, by the AMs, of eosinophilic material. Whereas exposure to heat or H2O2 induced in all AMs the synthesis of the classical HSPs, in these two cases, we found spontaneous synthesis of HSPs and of a 32 kD oxidation-specific stress protein, haeme oxygenase (HO). Exposure of AM to purified eosinophil-derived proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), alone or in combination, did not induce stress protein synthesis, further suggesting that phagocytosis is involved in this induction. Stress protein synthesis by AMs may represent a new cellular marker of pulmonary injury and eosinophilic inflammation, and an autoprotective mechanism against oxidative stress.
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PMID:Spontaneous heat shock protein synthesis by alveolar macrophages in interstitial lung disease associated with phagocytosis of eosinophils. 849 Dec 97

Eosinophils have been shown to increase in tissues during many fibrotic conditions and consequently have been suggested to contribute to the development of fibrosis. This study tested the hypothesis that eosinophils are essential in the development of lung fibrosis in mice in response to bleomycin (BLM). Anti-IL-5 antibody was administered intraperitoneally into mice 2 h prior to endotracheal BLM inoculation and thereafter, every other day. Lung eosinophilia was evaluated by measurement of eosinophil peroxidase activity and confirmed by eosinophil counts in histologic sections. Lung fibrosis was evaluated by hydroxyproline content and confirmed by collagen staining in histological sections. Results demonstrated that BLM induced pronounced lung eosinophilia, which was maximal 7 days after BLM treatment and remained elevated through day 14, in C57B1/6 SCID mice and CBA/J mice. In contrast, eosinophilia was a minor component in the lungs of wildtype C57B1/6 mice after BLM treatment, although lung fibrosis developed similarly in all three strains of mice. Treatment with anti-IL-5 completely abrogated eosinophilia but failed to block pulmonary fibrosis induced by BLM in all mouse strains, including C57B1/6 SCID, wildtype C57B1/6 mice, and CBA/J mice. Analysis of cytokine mRNA by RNase-protection assay in C57B1/6 SCID mice indicated that BLM treatment caused enhanced expression of the cytokines, TNF-alpha, and IL-6 at days 3, 7, and 14 post-BLM inoculation, regardless of whether eosinophils were depleted by anti-IL-5. Finally, the importance of eosinophils in lung fibrosis was examined in IL-5 gene knockout mice (IL-5tm1Kopf). BLM treatment induced significant lung fibrosis in IL-5 knockout mice in the absence of eosinophilia. These findings indicate that eosinophils are not an absolute requirement for BLM-induced pulmonary fibrosis in the mouse.
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PMID:Bleomycin-induced pulmonary fibrosis is independent of eosinophils. 1103 73

Adenosine is a signaling molecule produced during conditions that cause cellular stress or damage. This signaling pathway is implicated in the regulation of pulmonary disorders through the selective engagement of adenosine receptors. The goal of this study was to examine the involvement of the A(3) adenosine receptor (A(3)R) in a bleomycin model of pulmonary inflammation and fibrosis. Results demonstrated that A(3)R-deficient mice exhibit enhanced pulmonary inflammation that included an increase in eosinophils. Accordingly, there was a selective up-regulation of eosinophil-related chemokines and cytokines in the lungs of A(3)R-deficient mice exposed to bleomycin. This increase in eosinophil numbers was accompanied by a decrease in the amount of extracellular eosinophil peroxidase activity in lavage fluid from A(3)R-deficient mice exposed to bleomycin, an observation suggesting that the A(3)R is necessary for eosinophil degranulation in this model. Despite an increase in inflammatory metrics associated with A(3)R-deficient mice treated with bleomycin, there was little difference in the degree of pulmonary fibrosis. Examination of fibrotic mediators demonstrated enhanced transforming growth factor (TGF)-beta1 expression, but not a concomitant increase in TGF-beta1 activity. This was associated with the loss of expression of matrix metalloprotease 9, an activator of TGF-beta1, in alveolar macrophages and airway mast cells in the lungs of A(3)R-deficient mice. Together, these results suggest that the A(3)R serves antiinflammatory functions in the bleomycin model, and is also involved in regulating the production of mediators that can impact fibrosis.
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PMID:A3 adenosine receptor signaling influences pulmonary inflammation and fibrosis. 1858 54