Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages

PloS One
Juanjuan ZhaoYoh Takuwa

Abstract

Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of the lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. We observed by using S1pr2LacZ/+ mice that S1PR2 was expressed in alveolar macrophages, vascular endothelial cells and alveolar epithelial cells in the lung and that S1PR2-expressing cells accumulated in the fibrotic legions. Bone marrow chimera experiments suggested that S1PR2 in bone marrow-derived cells contributes to the development of lung fibrosis. Depletion of macrophages greatly attenuated lung fibrosis. Bleomycin administration stimulated the mRNA expression of the profibrotic cytokines IL-13 and IL-4 and the M2 markers including arginase 1, Fizz1/Retnla, Ccl17 and Ccl24 in cells collected from broncho-alveolar lavage fluids (BALF), and S1pr2 deletion markedly diminished the stimulated expression of these genes. BALF cells from bleomycin-administered wild-type mice showed a marked increase in phosphorylation of STAT6, a transcription factor which is activated downstream of IL-13, compare...Continue Reading

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Dec 28, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Debra L LaskinJeffrey D Laskin
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Sep 8, 2021·Frontiers in Immunology·Amit Kishore, Martin Petrek

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Datasets Mentioned

BETA
GSE85411

Methods Mentioned

BETA
bronchoalveolar lavage
PCR
biopsies
Assay
fluorescence activated cell sorter
Feature Extraction
ELISA

Software Mentioned

BZ
Feature Extraction
II Analyzer
Prism
Image Gauge
ImageJ
GraphPad
GeneSpring GX12

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