PMID- 28714941 OWN - NLM STAT- MEDLINE DCOM- 20180426 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 7 DP - 2017 Jul 17 TI - Autophagy Induced FHL2 Upregulation Promotes IL-6 Production by Activating the NF-kappaB Pathway in Mouse Aortic Endothelial Cells after Exposure to PM2.5. LID - 10.3390/ijms18071484 [doi] LID - 1484 AB - Epidemiological and clinical studies have increasingly shown that fine particulate matter (PM2.5) is associated with cardiovascular morbidity and mortality, which share the common feature of PM2.5-induced vascular inflammation; however, the underlying mechanisms of how PM2.5 triggers increased inflammatory response in vascular endothelial cells are not well understood. After treating mouse aortic endothelial cells (MAECs) with different concentrations of PM2.5, we assessed interleukin (IL)-6 and four and a half LIM domains 2 (FHL2) expression in cell supernatant by enzyme-linked immunosorbent assay and Western blot, respectively, as well as activation of nuclear factor (NF)-kappaB and immune-response signaling pathways. Additionally, changes in pathway activation, IL-6 expression, and autophagy were evaluated under PM2.5 exposure, following FHL2 knockdown with small interfering RNA. Our results indicated that PM2.5 exposure induced FHL2 expression and IL-6 secretion, as well as activation of pathways associated with immune response. Additionally, following FHL2 knockdown, the activation of NF-kappaB-related pathways and IL-6 secretion was inhibited under PM2.5 exposure, although the Akt- and p38-signaling pathways were not affected. Furthermore, PM2.5 exposure induced autophagy, whereas autophagy inhibition eventually inhibited PM2.5-induced FHL2 expression. These findings suggested a novel link between autophagy induced FHL2 upregulation and IL-6 production in MAECs under PM2.5 exposure. FAU - Xia, Wen-Rong AU - Xia WR AD - Laboratory of Genomic Engineering, Beijing Institute of Basic Medical Sciences, Beijing 100000, China. xiawenrong@sina.com. FAU - Fu, Wenliang AU - Fu W AD - Laboratory of Genomic Engineering, Beijing Institute of Basic Medical Sciences, Beijing 100000, China. fwl86@139.com. FAU - Wang, Qin AU - Wang Q AD - Institute for Environmental Health and Related Product Safety, Chinese center for disease control, Beijing 100000, China. wangqinbj@163.com. FAU - Zhu, Xiaoming AU - Zhu X AD - Laboratory of Genomic Engineering, Beijing Institute of Basic Medical Sciences, Beijing 100000, China. kitty66cat@126.com. FAU - Xing, Wei-Wei AU - Xing WW AD - Laboratory of Genomic Engineering, Beijing Institute of Basic Medical Sciences, Beijing 100000, China. huozinangua@163.com. FAU - Wang, Min AU - Wang M AD - Laboratory of Genomic Engineering, Beijing Institute of Basic Medical Sciences, Beijing 100000, China. wmmm12@sina.cn. FAU - Xu, Dong-Qun AU - Xu DQ AD - Institute for Environmental Health and Related Product Safety, Chinese center for disease control, Beijing 100000, China. dongqunxu@126.com. FAU - Xu, Dong-Gang AU - Xu DG AD - Laboratory of Genomic Engineering, Beijing Institute of Basic Medical Sciences, Beijing 100000, China. xudg@bmi.ac.cn. LA - eng PT - Journal Article DEP - 20170717 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Fhl2 protein, mouse) RN - 0 (Interleukin-6) RN - 0 (LIM-Homeodomain Proteins) RN - 0 (Muscle Proteins) RN - 0 (NF-kappa B) RN - 0 (Particulate Matter) RN - 0 (Transcription Factors) RN - 0 (interleukin-6, mouse) SB - IM MH - Animals MH - Aorta/*cytology/drug effects/immunology MH - Autophagy MH - Cell Survival/drug effects MH - Endothelial Cells/cytology/drug effects/immunology MH - Gene Knockdown Techniques MH - Interleukin-6/*metabolism MH - LIM-Homeodomain Proteins/genetics/*metabolism MH - Mice MH - Muscle Proteins/genetics/*metabolism MH - NF-kappa B/*metabolism MH - Particulate Matter/*toxicity MH - Signal Transduction MH - Transcription Factors/genetics/*metabolism MH - Transcriptional Activation MH - *Up-Regulation PMC - PMC5535974 OTO - NOTNLM OT - FHL2 OT - IL-6 OT - NF-kappaB OT - PM2.5 OT - autophagy OT - mouse aortic endothelial cells COIS- The authors declare no conflicts of interest. EDAT- 2017/07/18 06:00 MHDA- 2018/04/27 06:00 PMCR- 2017/07/01 CRDT- 2017/07/18 06:00 PHST- 2017/06/06 00:00 [received] PHST- 2017/06/30 00:00 [revised] PHST- 2017/07/07 00:00 [accepted] PHST- 2017/07/18 06:00 [entrez] PHST- 2017/07/18 06:00 [pubmed] PHST- 2018/04/27 06:00 [medline] PHST- 2017/07/01 00:00 [pmc-release] AID - ijms18071484 [pii] AID - ijms-18-01484 [pii] AID - 10.3390/ijms18071484 [doi] PST - epublish SO - Int J Mol Sci. 2017 Jul 17;18(7):1484. doi: 10.3390/ijms18071484.