NLRP3 deletion inhibits inflammation-driven mouse lung tumorigenesis induced by benzo(a)pyrene and lipopolysaccharide.

Abstract

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:

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:

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:

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.

• Authors: Li Huang, Shuyin Duan, Hua Shao, Aihua Zhang, Shuang Chen, Peng Zhang, Na Wang, Wei Wang, Yongjun Wu, Jing Wang, Hong Liu, Wu Yao, Qiao Zhang, Feifei Feng
• Journal: Respiratory research (Respir Res) Vol. 20 Issue 1 Pg. 20 (Jan 29 2019) ISSN: 1465-993X [Electronic] England
• PMID: 30696442 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Benzo(a)pyrene

Topics

• Animals
• Benzo(a)pyrene (toxicity)
• Carcinogenesis (chemically induced, metabolism, pathology)
• Female
• Lipopolysaccharides (toxicity)
• Lung Neoplasms (chemically induced, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NLR Family, Pyrin Domain-Containing 3 Protein (deficiency)