NLRP3 deletion inhibits inflammation-driven mouse lung tumorigenesis induced by benzo(a)pyrene and lipopolysaccharide.
Benzo(a)pyrene
Inflammation
Lipopolysaccharide
Lung tumorigenesis
NLRP3
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
29 Jan 2019
29 Jan 2019
Historique:
received:
06
10
2018
accepted:
13
01
2019
entrez:
31
1
2019
pubmed:
31
1
2019
medline:
19
3
2019
Statut:
epublish
Résumé
Inflammatory micro-environment has been proposed to play a critical role in lung tumorigenesis. NLRP3 is known as an intracellular receptor involving inflammation and has been reported which is increasingly associated with tumor development, but the role in inflammation-driven lung cancer has not been fully clarified. In this study, we investigated whether lipopolysaccharide (LPS)-induced pulmonary inflammation could contribute to lung tumorigenesis induced by benzo(a)pyrene [B(a)p] in C57BL/6J mice and the role of NLRP3 in the pathogenesis. NLRP3-/- mice and C57BL/6J mice (wide-type, WT) were instilled intratracheally with B(a)p (1 mg/mouse) once a week for 4 times [the week of the last time of B(a)p treatment named Week 0], and mice were then instilled intratracheally with LPS at Week 3, 2.5 μg/mouse, once every three weeks for 5 times. At Week 30, the incidence, number, size and histopathology of lung tumor were analyzed. Mice exposed to B(a)p or B(a)p plus LPS could induce lung tumors, whereas LPS or vehicles treatment could not induce lung tumorigenesis. In WT mice, B(a)p plus LPS exposure significantly increased tumor incidence, mean tumor count and tumor size of visible tumors of lungs compared with B(a)p treatment alone, and NLRP3 deletion inhibited lung tumorigenesis induced by B(a)p or B(a)p plus LPS. Histopathological examination found LPS-induced pulmonary inflammatory changes enhanced lung tumorigenesis induced by B(a)p in WT mice, deletion of NLRP3 improved the inflammatory changes induced by LPS and the number and size of pathological tumor nests induced by B(a)p or B(a)p plus LPS. In addition, we found B(a)p treatment and B(a)p plus LPS treatment predominately induced the development of adenoma. LPS enhanced B(a)p-induced lung tumorigenesis in WT and NLRP3-/- mice of C57BL/6J strain, and NLRP3 deletion inhibits lung tumorigenesis induced by B(a)p or B(a)p plus LPS.
Sections du résumé
BACKGROUND
BACKGROUND
Inflammatory micro-environment has been proposed to play a critical role in lung tumorigenesis. NLRP3 is known as an intracellular receptor involving inflammation and has been reported which is increasingly associated with tumor development, but the role in inflammation-driven lung cancer has not been fully clarified. In this study, we investigated whether lipopolysaccharide (LPS)-induced pulmonary inflammation could contribute to lung tumorigenesis induced by benzo(a)pyrene [B(a)p] in C57BL/6J mice and the role of NLRP3 in the pathogenesis.
METHODS
METHODS
NLRP3-/- mice and C57BL/6J mice (wide-type, WT) were instilled intratracheally with B(a)p (1 mg/mouse) once a week for 4 times [the week of the last time of B(a)p treatment named Week 0], and mice were then instilled intratracheally with LPS at Week 3, 2.5 μg/mouse, once every three weeks for 5 times. At Week 30, the incidence, number, size and histopathology of lung tumor were analyzed.
RESULTS
RESULTS
Mice exposed to B(a)p or B(a)p plus LPS could induce lung tumors, whereas LPS or vehicles treatment could not induce lung tumorigenesis. In WT mice, B(a)p plus LPS exposure significantly increased tumor incidence, mean tumor count and tumor size of visible tumors of lungs compared with B(a)p treatment alone, and NLRP3 deletion inhibited lung tumorigenesis induced by B(a)p or B(a)p plus LPS. Histopathological examination found LPS-induced pulmonary inflammatory changes enhanced lung tumorigenesis induced by B(a)p in WT mice, deletion of NLRP3 improved the inflammatory changes induced by LPS and the number and size of pathological tumor nests induced by B(a)p or B(a)p plus LPS. In addition, we found B(a)p treatment and B(a)p plus LPS treatment predominately induced the development of adenoma.
CONCLUSION
CONCLUSIONS
LPS enhanced B(a)p-induced lung tumorigenesis in WT and NLRP3-/- mice of C57BL/6J strain, and NLRP3 deletion inhibits lung tumorigenesis induced by B(a)p or B(a)p plus LPS.
Identifiants
pubmed: 30696442
doi: 10.1186/s12931-019-0983-4
pii: 10.1186/s12931-019-0983-4
pmc: PMC6352353
doi:
Substances chimiques
Lipopolysaccharides
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, mouse
0
Benzo(a)pyrene
3417WMA06D
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20Subventions
Organisme : the National Natural Science Foundation of China
ID : 81402712
Organisme : the outstanding youth grant of Zhengzhou University
ID : 1421329082
Organisme : the training grant of Zhengzhou University
ID : 2017ZDGGJS039
Organisme : the grant from Henan Department of Education
ID : 14A330001
Organisme : the grants from Henan Department of Science and Technology, China
ID : 162102310319
Organisme : the grants from Henan Department of Science and Technology, China
ID : 162102310602
Organisme : the program of scientific and technological innovation talents of Henan Province
ID : 154200510015
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