title: Porphyromonas gingivalis infected macrophages upregulate CD36 expression via ERK/NF-κB pathway.
abstract: CD36, a scavenger receptor, plays an important role in the progression of atherosclerosis through its interaction with oxidized low-density lipoprotein (ox-LDL). Porphyromonas gingivalis (P. gingivalis, Pg) has been shown to promote macrophage-derived foam cell formation by affecting the expression of CD36. However, the regulatory role of CD36 in macrophages infected with Pg remains largely unknown. Therefore, the aim of the present study was to explore the molecular mechanism of Pg induced CD36 expression in macrophages. Our results showed that Pg promoted ox-LDL uptake by macrophages and the formation of foam cells. Pg infection increased CD36 mRNA and protein levels in ox-LDL-untreated macrophages. Moreover, small interferon RNA (siRNA) targeting CD36 significantly reduced foam cell formation induced by Pg. Additionally, Pg stimulated nuclear translocation of p65, which directly bound to the promoters of CD36 to facilitate its transcription. Inhibition of p65, NF-κB or ERK1/2 blocked Pg-induced CD36 production; whereas, overexpression of NF-κB subunits p65 and p50 upregulated CD36. Furthermore, Ras inhibitors significantly attenuated ERK1/2 activation and CD36 expression. Taken together, the data indicated that stimulation of the ERK/NF-κB pathway by Pg led to transactivation of the CD36 promoters, thereby upregulating CD36 expression in the infected macrophages. These findings may help design new treatment strategies in atherosclerosis.
authors.affiliation: Clinical Research Center, Shanghai Jiading Central Hospital, Shanghai 201800, China.
authors.forename: Dong-Yu
authors.initials: DY
authors.lastname: Liang
authors.affiliation: Shanghai Key Laboratory of Mycobacterium Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Mycobacterium Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
authors.forename: Jian-Xia
authors.initials: JX
authors.lastname: Chen
authors.affiliation: Clinical Research Center, Shanghai Jiading Central Hospital, Shanghai 201800, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: He
authors.affiliation: Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of Mycobacterium Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Bao-Xue
authors.initials: BX
authors.lastname: Ge
authors.affiliation: Clinical Research Center, Shanghai Jiading Central Hospital, Shanghai 201800, China. Electronic address: juneluo@yeah.net.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Luo
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005487:Foam Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D018955:CD36 Antigens; D016328:NF-kappa B; D021122:Protein Subunits
keywords: CD36; ERK1/2; Macrophages; NF-κB; Ox-LDL; Porphyromonas gingivalis