Leitinger, Norbert

Norbert  Leitinger

Norbert Leitinger

Primary Appointment

Associate Professor, Pharmacology


  • PhD, University of Vienna

Contact Information

1340 Jefferson Park Ave., Jordan Hall, Room 5039A
Charlottesville, VA 22908
Telephone: 434-243-6363
Fax: 434-982-3878
Email: nl2q@virginia.edu

Research Interests

Role of lipid oxidation products in inflammation and vascular immunology in atherosclerosis and diabetes

Research Description

Research Interests: Role of lipid oxidation products in inflammation and vascular immunology in atherosclerosis

and diabetes.

1. Resolution of acute and propagation of chronic inflammation.

2. Mechanisms of endothelial-monocyte interaction in chronic inflammation.

3. Intracellular signaling induced by oxidized lipids.

4. Pattern recognition in innate immunity (Toll like receptors).

5. Antiinflammatory activities of PPARs.

6. Regulation of heme oxygenase-1.

Techniques in Use: Quantitative RT-PCR, Promoter-reporter assays, Gel shift, siRNA, Transfection,

HPLC and ESI-MS, TLC, Cell culture, Immunohistochemistry, Flow cytometry, SDS-PAGE,

Western blotting, Mouse models of inflammation.

Current Summary: Inflammation is generally accompanied by tissue damage associated with oxidation

of host macromolecules by inflammation-derived free radicals. Recent evidence

suggests that phospholipid oxidation products (OxPL), which are generated by

oxidation of cellular membranes, lipoproteins and during apoptosis, represent

danger signals that modulate inflammation and the activation of the innate immune

response. My laboratory has recently demonstrated that certain OxPL are potent

negative feedback regulators of innate immune responses via blocking the interaction

of endotoxin with its Toll-like receptor-4 (TLR-4). Ongoing projects aim to

1) identify mechanisms by which OxPL modulate a specific immune response and

delineate pathways that determine the signal differentiation between OxPL (altered

self) and pathogen-associated molecular patterns (PAMPs) such as LPS (non-self),

2) investigate how acute inflammation is resolved or driven into a chronic state

by OxPL, and 3) examine how monocyte specificity is brought about in chronic

inflammation. The long-term goals of this research are to understand how oxidative

modification of lipids during tissue damage leads to an inadequate immune response

during infection, causes disruption of the tightly controlled balance of immune

tolerance, and ultimately provokes chronic inflammation.

Peroxisomal proliferator activated receptors (PPARs) are ligand-activated transcription

factors belonging to the superfamily of nuclear hormone receptors. In addition

to regulating the fatty acid and glucose metabolism in liver, myocardium and

adipose tissue, they have been shown to exert direct anti-inflammatory effects

in the vascular wall, although the underlying mechanisms are poorly understood.

Consequently PPAR ligands are able to slow down the progression of inflammatory

vascular diseases like atherosclerosis and restenosis. Currently, we investigate

the hypothesis that the induction of the potent anti-inflammatory gene heme

oxygenase-1 (HO-1) by PPARs in the vascular wall significantly contributes to

their anti-inflammatory effects.

Selected Publications