Dataset Information

The Crucial Role of PPAR?-Egr-1-Pro-Inflammatory Mediators Axis in IgG Immune Complex-Induced Acute Lung Injury.

ABSTRACT:

Background

The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) ? plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown.

Objectives

The study is designed to determine the effect of PPAR? on IgG-IC-triggered acute lung inflammation, and the underlying mechanisms, which might provide theoretical basis for therapy of acute lung inflammation.

Setting

Department of Pathogenic Biology and Immunology, Medical School of Southeast University.

Subjects

Mice with down-regulated/up-regulated PPAR? activity or down-regulation of Early growth response protein 1 (Egr-1) expression, and the corresponding controls.

Interventions

Acute lung inflammation is induced in the mice by airway deposition of IgG-IC. Activation of PPAR? is achieved by using its agonist Rosiglitazone or adenoviral vectors that could mediate overexpression of PPAR?. PPAR? activity is suppressed by application of its antagonist GW9662 or shRNA. Egr-1 expression is down-regulated by using the gene specific shRNA.

Measures and main results

We find that during IgG-IC-induced acute lung inflammation, PPAR? expression at both RNA and protein levels is repressed, which is consistent with the results obtained from macrophages treated with IgG-IC. Furthermore, both in vivo and in vitro data show that PPAR? activation reduces IgG-IC-mediated pro-inflammatory mediators' production, thereby alleviating lung injury. In terms of mechanism, we observe that the generation of Egr-1 elicited by IgG-IC is inhibited by PPAR?. As an important transcription factor, Egr-1 transcription is substantially increased by IgG-IC in both in vivo and in vitro studies, leading to augmented protein expression, thus amplifying IgG-IC-triggered expressions of inflammatory factors via association with their promoters.

Conclusion

During IgG-IC-stimulated acute lung inflammation, PPAR? activation can relieve the inflammatory response by suppressing the expression of its downstream target Egr-1 that directly binds to the promoter regions of several inflammation-associated genes. Therefore, regulation of PPAR?-Egr-1-pro-inflammatory mediators axis by PPAR? agonist Rosiglitazone may represent a novel strategy for blockade of acute lung injury.

SUBMITTER: Yan C

PROVIDER: S-EPMC7947684 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

The Crucial Role of PPARγ-Egr-1-Pro-Inflammatory Mediators Axis in IgG Immune Complex-Induced Acute Lung Injury.

Yan Chunguang C Chen Jing J Ding Yue Y Zhou Zetian Z Li Bingyu B Deng Chunmin C Yuan Dong D Zhang Qi Q Wang Ximo X

Frontiers in immunology 20210225

<h4>Background</h4>The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown.<h4>Objectives</h4>The study is designed to determine the effect of PPARγ on IgG-IC-triggered acute lung inf ...[more]

PMID: 33717177

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