Crystalline Silica-induced Leukotriene B4-dependent Inflammation Promotes Lung Tumour Growth

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Apr 30

PMID 25923988

Citations 59

Authors

Shuchismita R Satpathy

Venkatakrishna R Jala

Sobha R Bodduluri

Elangovan Krishnan

Bindu Hegde

Gary W Hoyle

Mostafa Fraig

Andrew D Luster

Bodduluri Haribabu

Affiliations

Soon will be listed here.

Abstract

Chronic exposure to crystalline silica (CS) causes silicosis, an irreversible lung inflammatory disease that may eventually lead to lung cancer. In this study, we demonstrate that in K-ras(LA1) mice, CS exposure markedly enhances the lung tumour burden and genetic deletion of leukotriene B4 receptor-1 (BLT1(-/-)) attenuates this increase. Pulmonary neutrophilic inflammation induced by CS is significantly reduced in BLT1(-/-)K-ras(LA1) mice. CS exposure induces LTB4 production by mast cells and macrophages independent of inflammasome activation. In an air-pouch model, CS-induced neutrophil recruitment is dependent on LTB4 production by mast cells and BLT1 expression on neutrophils. In an implantable lung tumour model, CS exposure results in rapid tumour growth and decreased survival that is attenuated in the absence of BLT1. These results suggest that the LTB4/BLT1 axis sets the pace of CS-induced sterile inflammation that promotes lung cancer progression. This knowledge may facilitate development of immunotherapeutic strategies to fight silicosis and lung cancer.

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