Smoking-Associated Carcinogen-Induced Inflammation Promotes Lung Carcinogenesis via IRAK4 Activation.

ABSTRACT:

Purpose

Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Two major carcinogens in cigarette smoke, nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and benzo(α)pyrene (BaP), have not been tested in models that mimic inhaled exposure for prolonged periods of time.

Experimental design

Mouse models were used for intratracheal delivery of NNK and BaP (NB) for 18 months. Tissue microarrays from human lung cancers were evaluated for IL-1 receptor-associated kinase-4 (IRAK4) expression. Functional effects of IRAK4 inhibition were evaluated in cell lines and xenografts.

Results

Smoking-associated carcinogen-tre

SUBMITTER: Aggarwal RK 

PROVIDER: S-EPMC11832316 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature