Gut Microbiota-Derived PGF2α Fights against Radiation-Induced Lung Toxicity through the MAPK/NF-κB Pathway.

Zhi-Yuan Chen,Ming Cui,Sai-Jun Fan,Hui-Wen Xiao,Jia-Li Dong,Yuan Li,Bin Wang

doi:10.3390/antiox11010065

Abstract

Radiation pneumonia is a common and intractable side effect associated with radiotherapy for chest cancer and involves oxidative stress damage and inflammation, prematurely halting the remedy and reducing the life quality of patients. However, the therapeutic options for the complication have yielded disappointing results in clinical application. Here, we report an effective avenue for fighting against radiation pneumonia. Faecal microbiota transplantation (FMT) reduced radiation pneumonia, scavenged oxidative stress and improved lung function in mouse models. Local chest irradiation shifted the gut bacterial taxonomic proportions, which were preserved by FMT. The level of gut microbiota-derived PGF2α decreased following irradiation but increased after FMT. Experimental mice with PGF2α replenishment, via an oral route, exhibited accumulated PGF2α in faecal pellets, peripheral blood and lung tissues, resulting in the attenuation of inflammatory status of the lung and amelioration of lung respiratory function following local chest irradiation. PGF2α activated the FP/MAPK/NF-κB axis to promote cell proliferation and inhibit apoptosis with radiation challenge; silencing MAPK attenuated the protective effect of PGF2α on radiation-challenged lung cells. Together, our findings pave the way for the clinical treatment of radiotherapy-associated complications and underpin PGF2α as a gut microbiota-produced metabolite.

Highlights

Lung cancer morbidity and mortality rank first among malignant tumours worldwide [1]
The respiratory quotient (RQ) value increased after faecal microbiota transplantation (FMT) and decreased the VO2 intake but did not change
The results revealed that prostaglandin F2α (PGF2α) accumulated in the three samples after oral gavage (Figure 5B and Figure S2A,B), implying that PGF2α might play a role in lung tissues

Summary

Introduction

Lung cancer morbidity and mortality rank first among malignant tumours worldwide [1]. Radiotherapy plays a necessary role in the primary and adjuvant treatment of lung cancer, normal lung tissue outside the tumour is sensitive to ionizing radiation and is susceptible to harmful effects, including radiation pneumonia and lung fibrosis [4,5,6] and oxidative stress damage. Radiation-induced pneumonitis is characterized by the appearance of a large number of inflammatory cells causing inflammation [8]. After two weeks of radiation treatment, DNA oxidative damage and TGF-β1 (transforming growth factor-β) secretion increase, and other related factors aggravate the inflammatory response [9,10]

Objectives

Methods

Results

Conclusion