Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify changes in gene expression associated with emphysema, differential display was used to compare RNA extracted from emphysematous lung with that of unused donor tissue taken at the time of transplant. Two expressed clones with sequence homology to the 3' UTR of the murine flotillin-1 cDNA were identified. Flotillin-1 is a plasma membrane protein, which has been associated with detergent-insoluble glycolipid-rich domains and the formation of caveolae. One clone was 95 bp longer than the other. It arose from the use of a second polyadenylation signal and its existence was not due to differential expression nor to polymorphisms in the human flotillin-1 sequence. The 1839 bp human flotillin-1 sequence was completed by 5' RACE from a lung cDNA library. The human mRNA has a 1.9 kbase transcript being highly expressed in brain, heart and lung. The single copy flotillin-1 gene is located at 6p21.3 in the MHC class I region and consists of 13 exons over 15 kb. The ORF encodes a 427 residue protein with a molecular mass 47355 Da, and an isoelectric point 7.08. Human flotillin-1 has a 98% identity with the murine protein and a 47% identity with human flotillin-2. Flotillin-1 belongs to the Band 7.2/stomatin protein family, possessing a hydrophobic N-terminal region, predicted to form a single, outside to inside, transmembrane domain. The long central alpha-helical domain may form a coiled-coil. We have isolated and characterised a cDNA encoding the human flotillin-1 gene, which may play an important role in raft formation.
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PMID:Flotillin-1: gene structure: cDNA cloning from human lung and the identification of alternative polyadenylation signals. 1116 32

Cigarette smoke (CS) exposure is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic peribronchial, perivascular, and alveolar inflammation. The inflammatory cells consist primarily of macrophage, neutrophils, and lymphocytes. Although myeloid cells are well studied, the role of lymphocyte populations in pathogenesis of COPD remains unclear. Using a mouse model of CS-induced emphysema, our laboratory has previously demonstrated that CS exposure causes changes in the TCR repertoire suggestive of an Ag-specific response and triggers a pathogenic T cell response sufficient to cause alveolar destruction and inflammation. We extend these findings to demonstrate that T cells from CS-exposed mice of the BALB/cJ or C57B6 strain are sufficient to transfer pulmonary pathology to CS-naive, immunosufficient mice. CS exposure causes a proinflammatory phenotype among pulmonary T cells consistent with those from COPD patients. We provide evidence that donor T cells from CS-exposed mice depend on Ag recognition to transfer alveolar destruction using MHC class I-deficient recipient mice. Neither CD4(+) nor CD8(+) T cells from donor mice exposed to CS alone are sufficient to cause inflammation or pathology in recipient mice. We found no evidence of impaired suppression of T cell proliferation among regulatory T cells from CS-exposed mice. These results suggest that CS exposure initiates an Ag-specific response that leads to pulmonary destruction and inflammation that involves both CD8(+) and CD4(+) T cells. These results are direct evidence for an autoimmune response initiated by CS exposure.
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PMID:Functional characterization of T cell populations in a mouse model of chronic obstructive pulmonary disease. 2326 60