# Organochlorine compound-induced alterations in adipocyte/macrophage crosstalk and effects on wound healing

> **NIH NIH R21** · MISSISSIPPI STATE UNIVERSITY · 2020 · $181,875

## Abstract

Project Summary:
 The prevalence of obesity and type 2 diabetes are increasing at an alarming rate both within the United
States and worldwide. One of the most prevalent sequalae associated with type 2 diabetes is alterations in
wound healing which predispose the diabetic patient to diabetic foot ulceration and other soft tissue infections.
Within these infections, Staphylococcus aureus is the most commonly isolated bacterial species and is thought
to exacerbate diabetes-induced deficits in wound healing. While hyperglycemia and decreased peripheral
circulation have been implicated in diabetes-induced deficits in wound healing, the role of environmental
exposures remains unexplored. Recent studies have demonstrated environmental exposures to persistent
organic pollutants (POPs), including legacy organochlorine (OC) pesticides, may promote type 2 diabetes
pathogenesis and that these compounds may have immunomodulatory effects such as altering macrophage
polarization and adipocyte secretion of adipokines. Additionally, POPs and especially OC pesticide based POPs
bioaccumulate in the subcutaneous adipose tissue where they may exert a localized effect to alter the adipose
tissue microenvironment. Our current preliminary data demonstrate exposure to the prevalent OC pesticide
metabolites dichlorodiphenyldichloroethylene (DDE) and oxychlordane have opposing effects on macrophage
phagocytic activity. However, when DDE and oxychlordane exposure is in the context of an environmentally
relevant mixture, there is a significant mixture based effect which potentiates phagocytic activity at low
concentrations but decreases phagocytic activity with increasing concentrations. Therefore, the possibility arises
that OC pesticide increased POPs exposure may alter macrophage/adipocyte cross-talk in the adipose tissue
microenvironment which could alter wound healing kinetics. Our current hypothesis is exposure to the highly
prevalent POPs, DDE, trans-nonachlor, and oxychlordane will change the adipose tissue microenvironment
leading to altered macrophage function/plasticity which may have a deleterious effect on wound healing. This
hypothesis will be tested in the following specific aims: 1. Determine the effects of OC pesticide POPs exposure
on adipocyte/macrophage cross-talk and subsequent function to evaluate alterations in adipose tissue
microenvironment. 2. Determine the effects of exposure to OC pesticide POPs on the ability of S. aureus to
cause localized skin and soft tissue infection in normal and obese/type 2 diabetic mice. This will be the first
study to our knowledge to examine the effects of OC pesticide POPs exposure on the adipocyte/macrophage
cross-talk in the adipose tissue microenvironment with an emphasis on alterations in wound healing. Should
POPs significantly alter the adipose tissue microenvironment and wound healing, these compounds could be
used as biomarkers to identify patients which are at increased risk for chronic wounds such as diabeti...

## Key facts

- **NIH application ID:** 10011821
- **Project number:** 5R21ES030786-02
- **Recipient organization:** MISSISSIPPI STATE UNIVERSITY
- **Principal Investigator:** George E Howell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $181,875
- **Award type:** 5
- **Project period:** 2019-09-07 → 2023-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011821

## Citation

> US National Institutes of Health, RePORTER application 10011821, Organochlorine compound-induced alterations in adipocyte/macrophage crosstalk and effects on wound healing (5R21ES030786-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10011821. Licensed CC0.

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