Pioglitazone Modifies Kupffer Cell Function and Protects Against -Induced Bacteremia in Burned Mice

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Nov 11

PMID 36361535

Authors

Hiromi Miyazaki

Manabu Kinoshita

Hiroyuki Nakashima

Shingo Nakamura

Daizoh Saitoh

Affiliations

Soon will be listed here.

Abstract

Infectious complications and subsequent sepsis in severely burned patients lead to high morbidity and mortality in response to uncontrolled innate immune responses mediated by macrophages. Peroxisome proliferator-activated receptor gamma (PPARγ) has anti-inflammatory activity and acts as a master regulator of macrophage polarization. In this study, we investigated whether the administration of a PPARγ agonist could modulate the Kupffer cell phenotype and thereby ameliorate the dysregulated innate response during post-burn bacterial infection. C57BL/6 mice were subjected to severe burns and randomized to receive either the PPARγ agonist, pioglitazone, or the vehicle control five days after injury, followed by the subsequent analysis of hepatic macrophages. Survival from the bacterial infection was monitored for seven days. Pioglitazone protected burned mice against bacterial infection. A single treatment with pioglitazone significantly enhanced phagocytosis, phagosome acidification, bacterial clearance, and reduction in inflammatory mediators in Kupffer cells. In conclusion, PPARγ activation by pioglitazone prevents clinical deterioration due to post-burn bacterial infection and improves survival. Our findings suggest that pioglitazone may be an effective therapeutic candidate for post-burn infectious complications.

Citing Articles

The roles of tissue-resident macrophages in sepsis-associated organ dysfunction.

Gao Y, Tian X, Zhang X, Milebe Nkoua G, Chen F, Liu Y Heliyon. 2023; 9(11):e21391.

PMID: 38027963 PMC: 10643296. DOI: 10.1016/j.heliyon.2023.e21391.

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