The endotoxin (LPS) of Gram negative bacteria is a prototypic activator of the innate immune response. Recognition of LPS leads to upregulation of host defenses to limit infection, but may also lead to septic shock. Cells of myeloid lineage are central to this activation. Monocytes or macrophages (Mo) produce numerous inflammatory mediators including cytokines, bioactive lipids, degradative enzymes etc. In the case of cytokines, LPS induces gene expression via signaling pathways which are not well defined but appear to include serine/threonine kinases known as MAP kinases. It is proposed to study the role of one group of MAP kinases, p38, since they have been implicated in LPS-induced production of IL-1 and TNF. The major focus will be to identify substrates of p38 which control either transcriptional or post-transcriptional events associated with cytokine production. A combination of biochemical, immunologic and molecular biologic approaches will be used. These studies may lead to new approaches to control the injurious effects of LPS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041637-03
Application #
2887519
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Kraemer, Kristy A
Project Start
1997-07-01
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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