# VPO1 Protects from Endotoxin-Mediated Inflammation and Septic Shock

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $157,781

## Abstract

Project Summary
 Lipopolysaccharide (LPS), also known as endotoxin, is a component of Gram-negative
bacteria’s outer membrane. LPS induces an inflammatory response, severe endotoxin septic
shock. Sepsis poses a serious public health problem, with an overall mortality rate of 25-50%.
Vascular peroxidase-1 (VPO1), which is identified by the PI’s group, is new member of animal
heme-containing peroxidase family. VPO1 is unique in the family. It possesses five leucine-rich
repeats and four immunoglobulin domains in addition to the peroxidase domain. VPO1 is highly
expressed in cardiovascular system and the lung, and is secreted into blood, which is
approximate 1000-fold higher than myeloperoxidase in plasma. VPO1 also exists in
bronchoalveolar lavage fluid at relatively higher concentration. Our data show that VPO1
specifically interacts with LPS via its LRRs and Ig domains. Interestingly, administration of LPS
or Gram-negative bacteria causes more severe inflammatory response in VPO1-deficient mice
than in wild-type mice. We hypothesize that VPO1 mediates resistance to LPS-mediated
inflammatory response and septic shock by inhibiting the interaction of LPS and TLR4/MD-
2/CD14 co-receptor. The specific aim of the proposal is to extensively evaluate VPO1 roles in
LPS-mediated inflammatory response and septic shock. The in vitro and in vivo methods
including using VPO1-deficient mice will be carried out. Identification and characterization of
VPO1 role in protection from systemic inflammatory response and endotoxin shock will advance
new knowledge of innate immunity and inflammatory responses, which will ultimately lead to the
development of novel therapeutic strategies for endotoxin shock.

## Key facts

- **NIH application ID:** 9878043
- **Project number:** 5R21AI139900-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Guangjie Cheng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $157,781
- **Award type:** 5
- **Project period:** 2019-02-20 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878043

## Citation

> US National Institutes of Health, RePORTER application 9878043, VPO1 Protects from Endotoxin-Mediated Inflammation and Septic Shock (5R21AI139900-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878043. Licensed CC0.

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