Evaluation of diacetyl mediated pulmonary effects in physiologically relevant air-liquid interface models of human primary bronchial epithelial cells. (December 2019)

• Record Type: Journal Article
• Authors: Thimraj, Tania A.; Sompa, Shanzina I.; Ganguly, Koustav; Ernstgård, Lena; Johanson, Gunnar; Palmberg, Lena; Upadhyay, Swapna
• Is Part Of: Toxicology in vitro. Volume 61(2019)
• Publication Date: 2019-12
• Subjects: Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2019.104617
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Diacetyl is an artificial flavouring agent, known to cause bronchiolitis obliterans. Diacetyl-induced pulmonary effects were assessed in human primary bronchial epithelial cells (PBEC) cultured at air-liquid interface (ALI). The PBEC-ALI models were exposed to clean air (sham) and diacetyl vapour (1, 3, 10 and 30 ppm) for 30 min. At 6 and 24 h post-exposure, cell medium was sampled for assessment of cytotoxicity measurement, and CXCL8, MMP9 secretion by ELISA. Pro-inflammatory, oxidative stress, tissue injury/repair, anti-protease and beta-defensin markers were assessed using qRT-PCR. Additionally, epidermal growth factor receptor ligands (amphiregulin) and anti-protease (SLPI) were analysed at 6 h, 8 h and 24 h post exposure to 1 and 10 ppm diacetyl. No significant cytotoxicity was observed at any exposure level. MMP9 was significantly increased in both apical and basal media at 24 h. Both SLPI and amphiregulin secretion were significantly increased following exposure to 10 ppm diacetyl. Exposure of PBEC-ALI model to diacetyl vapour resulted in significantly altered transcript expression of pro-inflammatory, oxidative stress, anti-protease, tissue injury/repair markers. Changes in transcript expression of significantly altered markers were more prominent 24 h post-exposure compared to 6 h. This study warrants further mechanistic investigations to elucidate the pulmonary effects of inhaled diacetyl vapour using physiologically relevant in vitro models. Highlights: Multicellular ALI-model was used to study diacetyl mediated lung effects at occupationally relevant concentrations. Pro-inflammatory, oxidative stress, anti-protease, EGF receptor ligands and tissue injury markers were altered significantly. Multicellular ALI-models and gaseous exposure system are an advanced toxicity assessment tool to study the cell-cell interaction.