Expression and Regulation of a Disintegrin and Metalloproteinase (ADAM) 8 in Experimental Asthma
| Autor: | Marc E. Rothenberg, David P. Witte, Patricia C. Fulkerson, Nikolaos M. Nikolaidis, Samuel M. Pope, Nives Zimmermann, Anil Mishra, Nina E. King |
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| Rok vydání: | 2004 |
| Předmět: |
Pulmonary and Respiratory Medicine
Molecular Sequence Data Clinical Biochemistry Bronchi Mice Transgenic Respiratory Mucosa In situ hybridization Gene Expression Regulation Enzymologic Pathogenesis Mice Antigens CD medicine Disintegrin Animals Protein Isoforms RNA Messenger Lung Molecular Biology Mice Knockout Mice Inbred BALB C Metalloproteinase Interleukin-13 Base Sequence biology Membrane Proteins Metalloendopeptidases Interleukin Cell Biology Allergens respiratory system Asthma Protein Structure Tertiary Receptors Interleukin-4 respiratory tract diseases ADAM Proteins Alternative Splicing Disease Models Animal Ovalbumin medicine.anatomical_structure Immunology Trans-Activators biology.protein Interleukin-4 STAT6 Transcription Factor ADAM8 |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 31:257-265 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | Asthma, a complex chronic inflammatory pulmonary disorder, is on the rise despite intense ongoing research. To elucidate novel pathways involved in asthma pathogenesis, we used transcript expression profiling in a murine model of asthma. Employing asthma models induced by different allergens (ovalbumin and Aspergillus fumigatus) we uncovered the involvement of ADAM8, a member of a disintegrin and metalloproteinase (ADAM) family. In situ hybridization of mouse lungs revealed strong ADAM8 induction in peribronchial and perivascular inflammatory cells as well as in bronchiolar epithelial cells following allergen challenge. Sequence analysis of lung ADAM8 cDNA identified a novel splice variant of ADAM8 that contained an additional exon in juxtaposition to the transmembrane domain. Allergen-induced ADAM8 mRNA accumulation in the lung was dose- and time-dependent. Transgenic or pharmacologic delivery of interleukin (IL)-4 or IL-13 to the lungs resulted in a marked increase of ADAM8 expression. Gene-targeted mice studies revealed that ovalbumin-induced ADAM8 was largely dependent upon signal transducer and activator of transcription (STAT) 6 and the IL-4 receptor alpha-chain. Thus, ADAM8 is an allergen-, IL-4-, and IL-13-induced gene in the experimental asthmatic lung. Taken together with the role of ADAM33 in asthma, these results suggest that allergic lung responses involve the interplay of diverse members of the ADAM family. |
| Databáze: | OpenAIRE |
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