# Macrophage Redox State in Sterilizing and Injurious Inflammation

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $420,017

## Abstract

The current project is focused on the study of basic mechanisms of polarization of the innate immune
response. Macrophages are the primary cell type responsible for the polarization of the innate immunity
either by initiating and propagating inflammation (M1 phenotype) or resolving inflammation to promote
tissue healing (M2 phenotype). A relative new idea is that the dysregulation of macrophage polarization
with the prevalence of M1 over M2 phenotype promotes wide-spread inflammation and acute tissue
injury. In the case of lungs acute lung injury (ALI) may evolve to acute respiratory distress syndrome
(ARDS), a highly lethal form of respiratory failure. Hence, understanding the mechanisms by which
macrophages polarize into functionally distinct phenotypes may lead to new therapeutic strategies to
prevent or treat ARDS. Nuclear factor κB (NFκB) is a master regulator of inflammation being
responsible for the expression of genes that promote or resolve inflammation. While the p65/p50
configuration of NFκB promotes inflammation, the p50/p50 configuration promotes resolution. We
reason that these configurations also regulate how macrophages polarize into distinct phenotypes. In
this regard, we recently discovered that suppressor of cytokine signaling-1 (SOCS1) may operate the
switch in NFκB function since it targets nuclear p65 but not p50 to degradation changing the relative
abundances of these component subunits in the nucleus. The finding that SOCS1 is sensitive to
inhibition by nitric oxide (NO) and possibly other reactive species also indicate novel molecular
mechanisms by which SOCS1 activity, NFκB function, pro- and anti-inflammatory transcription, as well
as macrophage polarization and inflammatory outcomes are regulated. These mechanisms are the
focus of our three proposed aims: (1) to determine the mechanism by which SOCS1 promotes NFκB
functional switch from that of a pro- to that of an anti-inflammatory transcriptional complex; (2) to
determine if changes in the intracellular redox state of macrophages affects SOCS1 activity and NFκB
function as a transcription factor and (3) Determine how SOCS1 expression in different immune cell
types regulates the transition between inflammation propagation and resolution in a mouse model of
bacterial pneumonia.

## Key facts

- **NIH application ID:** 9894728
- **Project number:** 7R01AI131267-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Marcelo G. Bonini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,017
- **Award type:** 7
- **Project period:** 2017-04-07 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894728

## Citation

> US National Institutes of Health, RePORTER application 9894728, Macrophage Redox State in Sterilizing and Injurious Inflammation (7R01AI131267-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894728. Licensed CC0.

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