Lipoxin A4 may attenuate the progression of obesity-related glomerulopathy by inhibiting NF-κB and ERK/p38 MAPK-dependent inflammation.

Abstract

OBJECTIVES:

To investigate the effects of lipoxin A4 (LXA4) on inflammatory responses in obesity-related glomerulopathy (ORG) mouse model and its potential mechanisms.

METHODS:

Male C57BL/6 mice were randomly divided into 4 groups: normal, model, LXA4, and LXA4/Boc-2 groups (n = 8). Mice in LXA4 group were intraperitoneally injected with LXA4 (40 ng/kg) once daily for 3 days following 12 weeks of high-fat diet (HFD) feeding. LXA4 receptor antagonist, Boc-2, was administered in LXA4/Boc-2 group prior to LXA4 treatment to block the effects of LXA4. Renal morphology and function impairment were determined. Inflammation was tested by measuring serum and mRNA levels of pro-inflammatory cytokines and chemokines. HFD-induced activation of nuclear factor-kappa B (NF-κB) and phosphorylation of mitogen-activated protein kinases (MAPKs) were investigated by immunohistochemistry and western blot.

RESULTS:

HFD-feeding caused significant renal injury, pathological changes and inflammation in model group mice. LXA4 injection significantly alleviated HFD-induced effects on renal morphology and functions, as demonstrated by lower kidney index, glomerular diameter, 24 h urine protein, urinary albumin creatinine ratio and renal histomorphology. Moreover, HFD-induced accumulation of pro-inflammatory cytokines and chemokines were obviously attenuated by LXA4 administration, so did the HFD-induced activation of NF-κB and ERK/p38 MAPK pathways. However, these effects were markedly abrogated by BOC-2 pretreatment.

CONCLUSION:

LXA4 significantly attenuated HFD-induced renal inflammation and injury in ORG models, and these effects may be associated with the inhibition of activation of NF-κB and ERK/p38 MAPK pathways. The findings of our study may shed light on LXA4 showed a potential therapeutic application in ORG.

• Authors: Yan-Ping Guo, Hong-Kun Jiang, Hong Jiang, Hong-Yu Tian, Lei Li
• Journal: Life sciences (Life Sci) Vol. 198 Pg. 112-118 (Apr 01 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 29499280 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Enzyme Inhibitors
• I-kappa B Proteins
• Lipoxins
• NF-kappa B
• lipoxin A4
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Body Weight
• Diet, High-Fat
• Enzyme Inhibitors (therapeutic use)
• Enzyme-Linked Immunosorbent Assay
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• I-kappa B Proteins (metabolism)
• Inflammation (metabolism)
• Injections, Intraperitoneal
• Kidney Diseases (complications, metabolism)
• Kidney Glomerulus (pathology)
• Lipoxins (pharmacology)
• MAP Kinase Signaling System
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Obesity (complications, metabolism)
• Risk Factors
• p38 Mitogen-Activated Protein Kinases (metabolism)