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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
20049209 - Lung inflammation, injury, and proliferative response after repetitive particulate hexa...
16301759 - Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the lit...
15891109 - Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epith...
6302949 - Pulmonary macrophage phagocytosis and enzyme production after in vivo exposure to silic...
16086599 - Anti-inflammatory medications for cystic fibrosis lung disease: selecting the most appr...
21034489 - He3286, an oral synthetic steroid, treats lung inflammation in mice without immune supp...
15909119 - Ornithine decarboxylase prevents tumor necrosis factor alpha-induced apoptosis by decre...
11077999 - Cytokine responses of oral epithelial cells to porphyromonas gingivalis infection.
11063639 - Apoptosis may be an early event of progestin therapy for endometrial hyperplasia.
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    
Affiliation:
Department of Pathology, University of Vermont, 89 Beaumont Ave., Burlington, VT 05405, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD45 / metabolism
Asbestos, Serpentine / adverse effects*
Cell Proliferation
Gene Expression Regulation, Enzymologic
Inflammation
Interleukins / biosynthesis
Killer Cells, Natural / pathology
Lung Diseases / enzymology,  etiology*,  genetics*,  pathology
Lymphocyte Subsets / pathology
Macrophages / pathology
Mice
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
ID/Acronym/Agency:
P01 HL067004/HL/NHLBI NIH HHS; P01HL67004/HL/NHLBI NIH HHS; P30 CA022435/CA/NCI NIH HHS; P30CA22435/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Asbestos, Serpentine; 0/Interleukins; EC 2.7.11.13/Protein Kinase C-delta; EC 3.1.3.48/Antigens, CD45
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Expression of the metastasis suppressor KAI1 in decidual cells at the human maternal-fetal interface...
Next Document:  Pre-B-cell leukemia transcription factor 1 regulates expression of valosin-containing protein, a gen...