title: TLR4 mediates pneumolysin-induced ATF3 expression through the JNK/p38 pathway in Streptococcus pneumoniae-infected RAW 264.7 cells.
abstract: Activating transcription factor-3 (ATF3) acts as a negative regulator of cytokine production during Gram-negative bacterial infection. A recent study reported that ATF3 provides protection from Streptococcus pneumoniae infection by activating cytokines. However, the mechanism by which S. pneumoniae induces ATF3 after infection is still unknown. In this study, we show that ATF3 was upregulated via Toll-like receptor (TLR) pathways in response to S. pneumoniae infection in vitro. Induction was mediated by TLR4 and TLR2, which are in the TLR family. The expression of ATF3 was induced by pneumolysin (PLY), a potent pneumococcal virulence factor, via the TLR4 pathway. Furthermore, ATF3 induction is mediated by p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Thus, this study reveals a potential role of PLY in modulating ATF3 expression, which is required for the regulation of immune responses against pneumococcal infection in macrophages.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Cuong Thach
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Truc Thanh
authors.initials: TT
authors.lastname: Luong
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Rhee
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D002460:Cell Line; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000378:metabolism; D013301:Streptolysins / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D001426:Bacterial Proteins; D013301:Streptolysins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C032290:plY protein, Streptococcus pneumoniae
keywords: S. pneumoniae; Toll-like receptors (TLR); activating transcription factor-3 (ATF3); pneumococcal infection; pneumolysin (PLY)