# Ethanol modulate central and peripheral immune responses via HMGB1, IL-1Beta, and other Immune Signaling Molecules

> **NIH NIH K08** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $128,091

## Abstract

Project Summary/Abstract
Alcohol use disorders are third leading cause of preventable death, accounting for
approximately 90,000 preventable deaths each year (Danaei et al 2009). Nearly 50%
deaths are secondary to diseases that are associated with inflammation and aberrant
immune activation such as sepsis and alcoholic liver disease (Mokdad et al 2000).
Recent discoveries find that alcohol activates the innate immune system in both the
CNS and periphery. Thus, understanding the effects of alcohol on the immune system
is critical to form a foundation of discovery leading to the understanding of both the
pathology of alcoholism and numerous alcohol-associated diseases. We have found
recently that alcohol activates the innate immune system through the ‘master regulator’
of innate immunity, HMGB1. In this proposal we aim to investigate the effects of alcohol
on central and peripheral immune activation through HMGB1 and its companion
cytokine IL-. Using in vitro cell culture systems (Aim 1), in vivo experiments (Aim 2-3)
and assessments in human alcoholics, burn patients and alcoholic hepatitis patients
(Aim 4), we hope to gain an understanding of the immune effects of alcohol throughout
the body. I will gain new laboratory experience with real time-PCR, enzyme-linked
immunosorbant assays, co-immunoprecipitation, western blotting, intracerebral AAV5
viral injections, mass spectrometry, immunocytochemistry, and live fluorescent imaging.
We also investigate a novel mechanism of cell-cell communication in this pathology,
alcohol-induced release of pro-inflammatory microparticles. Further, we investigate the
role of the PTEN/PI3K/Akt/mTOR pathway in the immune effects of alcohol, and study
inhibitors of this pathway which may be novel therapeutic options. Our preliminary data
strongly suggest that alcohol causes central and peripheral HMGB1 and IL-1 release
in microparticles through a PTEN/PI3K/Akt/mTOR linked mechanism. This project also
incorporates substantial career development with career and research mentoring from
top tier researchers and clinicians, the learning of new experimental techniques, and
course work to enhance clinical/translational expertise. Co-mentors Fulton T. Crews,
PhD and Bruce Cairns MD provide a depth of basic science, clinical research, and
career development mentorship that will help ensure the successful transition of the
candidate to being a top independent translational researcher.

## Key facts

- **NIH application ID:** 9988985
- **Project number:** 5K08AA024829-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Leon Garland Coleman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $128,091
- **Award type:** 5
- **Project period:** 2017-09-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988985

## Citation

> US National Institutes of Health, RePORTER application 9988985, Ethanol modulate central and peripheral immune responses via HMGB1, IL-1Beta, and other Immune Signaling Molecules (5K08AA024829-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9988985. Licensed CC0.

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