Abstract

The primary focus of our research is to define the factors and signal transduction pathways involved in the modulation of human monocyte functions that may contribute to the immunopathology associated with various disease states. Connective tissue destruction is associated with many diseases in which the monocyte/macrophage is a prominent cell. Since matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are believed to play a major role in the destruction and remodeling of connective tissue, a major emphasis has been placed on how these enzymes and inhibitors are regulated. To address this question we are examining how biological mediators, such as cytokines, lipids and gram-negative bacterial, influence the mitogen-activated protein kinase and cyclooxygenase pathways involved in monocytge MMP and TIMP production. Current studies on the role of monocyte MMPs in various diseases have examined (a) how monocyte MT1-MMP may influence tumor metastasis through the activation of MMP-2 and (b) the impact of lipids, such as LDL and HDL, on monocyte MMP production as it relates to the immunopathology associated with atherosclerosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000456-14
Application #
6501687
Study Section
(IP)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Piao, Wenji; Song, Chang; Chen, Haiyan et al. (2008) Tyrosine phosphorylation of MyD88 adapter-like (Mal) is critical for signal transduction and blocked in endotoxin tolerance. J Biol Chem 283:3109-19
Hochman, Nira; Houri-Haddad, Yael; Koblinski, Jennifer et al. (2008) Cranberry juice constituents impair lymphoma growth and augment the generation of antilymphoma antibodies in syngeneic mice. Nutr Cancer 60:511-7
Zhang, Yahong; Zhou, Zhao-Hua; Bugge, Thomas H et al. (2007) Urokinase-type plasminogen activator stimulation of monocyte matrix metalloproteinase-1 production is mediated by plasmin-dependent signaling through annexin A2 and inhibited by inactive plasmin. J Immunol 179:3297-304
Medvedev, Andrei E; Piao, Wenji; Shoenfelt, Joanna et al. (2007) Role of TLR4 tyrosine phosphorylation in signal transduction and endotoxin tolerance. J Biol Chem 282:16042-53
Kim, Min P; Wahl, Larry M; Yanek, Lisa R et al. (2007) A monocyte chemoattractant protein-1 gene polymorphism is associated with occult ischemia in a high-risk asymptomatic population. Atherosclerosis 193:366-72
Philp, Deborah; Scheremeta, Brooke; Sibliss, Kedesha et al. (2006) Thymosin beta4 promotes matrix metalloproteinase expression during wound repair. J Cell Physiol 208:195-200
Devadas, Krishnakumar; Boykins, Robert A; Hardegen, Neil J et al. (2006) Selective side-chain modification of cysteine and arginine residues blocks pathogenic activity of HIV-1-Tat functional peptides. Peptides 27:611-21
Tripathi, Pulak; Madan, Rajat; Chougnet, Claire et al. (2006) An adenoviral vector for probing promoter activity in primary immune cells. J Immunol Methods 311:19-30
Mukundan, Lata; Bishop, Gail A; Head, Kimberly Z et al. (2005) TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages. J Immunol 174:1081-90
Lu, Yunbiao; Wahl, Larry M (2005) Oxidative stress augments the production of matrix metalloproteinase-1, cyclooxygenase-2, and prostaglandin E2 through enhancement of NF-kappa B activity in lipopolysaccharide-activated human primary monocytes. J Immunol 175:5423-9

Showing the most recent 10 out of 23 publications