Abstract

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.

  Funding Agency

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

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Lu, Jiawei; Wu, Xiurong; Hong, Mao et al. (2013) A potential suppressive effect of natural antisense IL-1? RNA on lipopolysaccharide-induced IL-1? expression. J Immunol 190:6570-8
Seit-Nebi, Alim; Cheng, Wei; Xu, Hong et al. (2012) MLK4 has negative effect on TLR4 signaling. Cell Mol Immunol 9:27-33
Zheng, Min; Wang, Yan-Hai; Wu, Xiao-Nan et al. (2011) Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1. Nat Cell Biol 13:263-72
Lee, Sangun; Wang, Yanhai; Kim, Sung Ouk et al. (2011) AMPD3 is involved in anthrax LeTx-induced macrophage cell death. Protein Cell 2:564-72
Wu, Xiao-Nan; Wang, Xue-Kun; Wu, Su-Qin et al. (2011) Phosphorylation of Raptor by p38beta participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation. J Biol Chem 286:31501-11
Hong, Lixin; Lai, Maoyi; Chen, Michelle et al. (2010) The miR-17-92 cluster of microRNAs confers tumorigenicity by inhibiting oncogene-induced senescence. Cancer Res 70:8547-57
Wu, Chia-Cheng; Wu, Xiaohua; Han, Jiahuai et al. (2010) p38? regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage. Protein Cell 1:573-83
Martins, Andrew; Han, Jiahuai; Kim, Sung O (2010) The multifaceted effects of granulocyte colony-stimulating factor in immunomodulation and potential roles in intestinal immune homeostasis. IUBMB Life 62:611-7
Ono, Koh; Wang, Xiaofei; Kim, Sung Ouk et al. (2010) Metaxin deficiency alters mitochondrial membrane permeability and leads to resistance to TNF-induced cell killing. Protein Cell 1:161-73
Kang, Young Jun; Otsuka, Motoyuki; van den Berg, Arjen et al. (2010) Epithelial p38alpha controls immune cell recruitment in the colonic mucosa. PLoS Pathog 6:e1000934

Showing the most recent 10 out of 56 publications