Premium
PM2.5 Increases Lung Inflammation through the Sirtuin‐SREBF1‐inflammasome Axis
Author(s) -
Tien ChiaPing
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb582
Subject(s) - inflammasome , inflammation , chemokine , sterol regulatory element binding protein , sirtuin , cxcl2 , immunology , biology , chemistry , microbiology and biotechnology , transcription factor , chemokine receptor , biochemistry , gene , acetylation
Epidemiological studies have shown that particulate matter (PM2.5) is strongly associated with inflammatory lung disease, including bronchitis, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. However, the mechanisms remain unclear. To identify the molecular targets of PM2.5, we analyzed transcriptomics data by microarray chips in human pulmonary fibroblasts (HPF) and human bronchial epithelial cells (HBEpic) after exposure to PM2.5. Through Genespring software to normalization, we have selected candidate targets for prediction potential upstream regulator and pathway by Ingenuity Pathway Analysis (IPA) that may be mediated the induction of lung inflammation. Our results showed sterol regulatory element‐binding transcription factor 1 (SREBF1) was the most significant upstream transcription regular in both PM2.5 added HPF and HBEpic cells. Through RT‐PCR and western blotting analysis, we validated SREBF1 and its downstream inflammasome genes, including interleukin 6 (IL‐6), C‐X‐C motif chemokine ligand 8 (CXCL8), BCL2 related protein A1 (BCL2A1), and heme oxygenase 1 (HMOX1) were activated after exposure to PM2.5 in vitro . In addition, our results also indicated Sirtuin pathway was significantly suppressed after PM2.5 treatment. Sirtuin1 was found to directly deacetylate SREBF1 to inhibit its function in inflammasome activity, which can be blocked by the addition of PM2.5. Furthermore, complementary experiments were performed, including the addition of Sirtuin1 recombinant protein or shRNAs of SREBF1 to PM2.5 exposed normal lung epithelial cells and fibroblasts. The results revealed that the activation of inflammasome genes expression could be significantly reversed. In conclusions, our results identify the Sirtuin‐SREBF1‐inflammasome axis may play a significant role in PM2.5‐induced pulmonary diseases and may provide novel therapeutic targets for patients. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .