Pioglitazone Modifies Kupffer Cell Function and Protects against Escherichia coli -Induced Bacteremia in Burned Mice.
Hiromi MiyazakiManabu KinoshitaHiroyuki NakashimaShingo NakamuraDaizoh SaitohPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- immune response
- escherichia coli
- insulin resistance
- high fat diet induced
- end stage renal disease
- ejection fraction
- chronic kidney disease
- risk factors
- induced apoptosis
- acute kidney injury
- intensive care unit
- newly diagnosed
- staphylococcus aureus
- type diabetes
- single cell
- open label
- metabolic syndrome
- clinical trial
- mouse model
- adipose tissue
- dendritic cells
- toll like receptor
- cell cycle arrest
- mesenchymal stem cells
- skeletal muscle
- drug induced
- randomized controlled trial
- inflammatory response
- cell therapy
- septic shock
- free survival
- multidrug resistant
- high glucose