Document Detail

Asbestos-induced peribronchiolar cell proliferation and cytokine production are attenuated in lungs of protein kinase C-delta knockout mice.
MedLine Citation:
PMID:  17200189     Owner:  NLM     Status:  MEDLINE    
The signaling pathways leading to the development of asbestos-associated diseases are poorly understood. Here we used normal and protein kinase C (PKC)-delta knockout (PKCdelta-/-) mice to demonstrate multiple roles of PKC-delta in the development of cell proliferation and inflammation after inhalation of chrysotile asbestos. At 3 days, asbestos-induced peribronchiolar cell proliferation in wild-type mice was attenuated in PKCdelta-/- mice. Cytokine profiles in bronchoalveolar lavage fluids showed increases in interleukin (IL)-1beta, IL-4, IL-6, and IL-13 that were decreased in PKCdelta-/- mice. At 9 days, microarray and quantitative reverse transcriptase-polymerase chain reaction analysis of lung tissues revealed increased mRNA levels of the profibrotic cytokine, IL-4, in asbestos-exposed wild-type mice but not PKCdelta-/- mice. PKCdelta-/- mice also exhibited decreased lung infiltration of polymorphonuclear cells, natural killer cells, and macrophages in bronchoalveolar lavage fluid and lung, as well as increased numbers of B lymphocytes and plasma cells. These changes were accompanied by elevated mRNA levels of immunoglobulin chains. These data show that modulation of PKC-delta has multiple effects on peribronchiolar cell proliferation, proinflammatory and profibrotic cytokine expression, and immune cell profiles in lung. These results also implicate targeted interruption of PKC-delta as a potential therapeutic option in asbestos-induced lung diseases.
Arti Shukla; Karen M Lounsbury; Trisha F Barrett; Joanna Gell; Mercedes Rincon; Kelly J Butnor; Douglas J Taatjes; Gerald S Davis; Pamela Vacek; Keiichi I Nakayama; Keiko Nakayama; Chad Steele; Brooke T Mossman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The American journal of pathology     Volume:  170     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-03     Completed Date:  2007-02-21     Revised Date:  2013-08-23    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  140-51     Citation Subset:  AIM; IM    
Department of Pathology, University of Vermont, 89 Beaumont Ave., Burlington, VT 05405, USA.
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MeSH Terms
Antigens, CD45 / metabolism
Asbestos, Serpentine / adverse effects*
Cell Proliferation
Gene Expression Regulation, Enzymologic
Interleukins / biosynthesis
Killer Cells, Natural / pathology
Lung Diseases / enzymology,  etiology*,  genetics*,  pathology
Lymphocyte Subsets / pathology
Macrophages / pathology
Mice, Inbred C57BL
Mice, Knockout
Protein Kinase C-delta / antagonists & inhibitors,  genetics*
Pulmonary Fibrosis / enzymology,  etiology,  genetics,  pathology
Signal Transduction / drug effects,  genetics
Grant Support
Reg. No./Substance:
0/Asbestos, Serpentine; 0/Interleukins; EC Kinase C-delta; EC, CD45

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