Abstract

The goal of this project is to elucidate key features of the expression and function of a new family of macrocyclic defensins termed theta -defensins expressed in primate myeloid cells. Rhesus theta defensin 1 (RTD-1) is prototype of this peptide family. The three specific aims are: 1) to characterize the constitutive and inducible expression of theta -defensin mRNAs and peptides in myeloid cells;2) to test the hypotheses that theta -defensins are delivered to the phagosome during cellular activation and to determine the contribution of these peptides to killing within the phagolysosome;3) to determine the molecular mechanism of theta -defensin-mediated bacterial killing. These studies should provide insights into the peptides. mechanism(s) of action, molecular basis of selectivity, and other potential interactions with host tissues or microbial structures.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI022931-24
Application #
7591050
Study Section
Special Emphasis Panel (NSS)
Program Officer
Korpela, Jukka K
Project Start
1989-07-01
Project End
2009-06-30
Budget Start
2009-04-01
Budget End
2009-06-30
Support Year
24
Fiscal Year
2009
Total Cost
$38,997
Indirect Cost

  Institution

Name
University of California Irvine
Department
Pathology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Schaal, Justin B; Maretzky, Thorsten; Tran, Dat Q et al. (2018) Macrocyclic ?-defensins suppress tumor necrosis factor-? (TNF-?) shedding by inhibition of TNF-?-converting enzyme. J Biol Chem 293:2725-2734
Basso, Virginia; Garcia, Angie; Tran, Dat Q et al. (2018) Fungicidal Potency and Mechanisms of ?-Defensins against Multidrug-Resistant Candida Species. Antimicrob Agents Chemother 62:
Oh, Young Taek; Tran, Dat; Buchanan, Thomas A et al. (2015) ?-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats. Am J Physiol Endocrinol Metab 309:E154-60
Tai, Kenneth P; Kamdar, Karishma; Yamaki, Jason et al. (2015) Microbicidal effects of ?- and ?-defensins against antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Innate Immun 21:17-29
Tongaonkar, Prasad; Trinh, Katie K; Schaal, Justin B et al. (2015) Rhesus macaque ?-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-?B and MAPK pathways. J Leukoc Biol 98:1061-70
Mastroianni, Jennifer R; Lu, Wuyuan; Selsted, Michael E et al. (2014) Differential Susceptibility of Bacteria to Mouse Paneth Cell ?-Defensins under Anaerobic Conditions. Antibiotics (Basel) 3:493-508
Tai, Kenneth P; Le, Valerie V; Selsted, Michael E et al. (2014) Hydrophobic determinants of ?-defensin bactericidal activity. Infect Immun 82:2195-202
Schaal, Justin B; Tran, Dat; Tran, Patti et al. (2012) Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis. PLoS One 7:e51337
Tongaonkar, Prasad; Golji, Amir E; Tran, Patti et al. (2012) High fidelity processing and activation of the human ?-defensin HNP1 precursor by neutrophil elastase and proteinase 3. PLoS One 7:e32469
Mastroianni, Jennifer R; Costales, Jessica K; Zaksheske, Jennifer et al. (2012) Alternative luminal activation mechanisms for paneth cell ?-defensins. J Biol Chem 287:11205-12

Showing the most recent 10 out of 84 publications