Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 170, Issue 1, Pages 140-151Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2007.060381
Keywords
-
Categories
Funding
- NATIONAL CANCER INSTITUTE [P30CA022435] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL067004] Funding Source: NIH RePORTER
- NCI NIH HHS [P30CA22435, P30 CA022435] Funding Source: Medline
- NHLBI NIH HHS [P01HL67004, P01 HL067004] Funding Source: Medline
Ask authors/readers for more resources
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 (PKC delta(-/-)) 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 PKC delta(-/-) mice. Cytokine profiles in bronchoalveolar lavage fluids showed increases in interleukin (IL)-1 beta, IL-4, IL-6, and IL-13 that were decreased in PKC delta(-/-) 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 wildtype mice but not PKC delta(-/-) mice. PKC delta(-/-) 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available