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Phloretin attenuates LPS-induced acute lung injury in mice via modulation of the NF-κB and MAPK pathways
- Source :
- International Immunopharmacology. 40:98-105
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Phloretin, which can be isolated from apple trees, has demonstrable anti-inflammatory and anti-oxidant effects in macrophages. We previously reported that phloretin could inhibit the inflammatory response and reduce intercellular adhesion molecule 1 (ICAM-1) expression in interleukin (IL)-1β-activated human lung epithelial cells. In the present study we now evaluate whether phloretin exposure could ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. Intra-peritoneal injections of phloretin were administered to mice for 7 consecutive days, prior to the induction of lung injury by intra-tracheal administration of LPS. Our subsequent analyses demonstrated that phloretin could significantly suppress LPS-induced neutrophil infiltration of lung tissue, and reduce the levels of IL-6 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid. We also found that phloretin modulated myeloperoxidase activity and superoxide dismutase activity, with decreased gene expression levels for chemokines, proinflammatory cytokines, and ICAM-1 in inflamed lung tissue. Phloretin also significantly reduced the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), thus limiting the inflammatory response, while promoting expression of heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2, both of which are cytoprotective. Our findings suggest that, mechanistically, phloretin attenuates the inflammatory and oxidative stress pathways that accompany lung injury in mice via blockade of the NF-κB and MAPK pathways.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Lipopolysaccharide
Phloretin
medicine.medical_treatment
Acute Lung Injury
Immunology
Anti-Inflammatory Agents
Lung injury
Pharmacology
Antioxidants
Proinflammatory cytokine
Leukocyte Count
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Animals
Immunology and Allergy
Lung
Peroxidase
Mice, Inbred BALB C
Superoxide Dismutase
business.industry
NF-kappa B
technology, industry, and agriculture
Membrane Proteins
Heme oxygenase
030104 developmental biology
Cytokine
Neutrophil Infiltration
chemistry
030220 oncology & carcinogenesis
Cytokines
Female
Tumor necrosis factor alpha
Mitogen-Activated Protein Kinases
business
Bronchoalveolar Lavage Fluid
Heme Oxygenase-1
Subjects
Details
- ISSN :
- 15675769
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- International Immunopharmacology
- Accession number :
- edsair.doi.dedup.....d4fd2776f5ccd88393d8263c3ba28314