title: Mycobacterial 3-hydroxyacyl-l-thioester dehydratase Y derived from Mycobacterium tuberculosis induces COX-2 expression in mouse macrophages through MAPK-NF-κB pathway.
abstract: Tuberculosis (TB) is a leading cause of global mortality due to infectious diseases. Expression of cyclooxygenase-2 (COX-2) acts as an important influencing factor favoring bacillary survival during TB infection. In this study, we investigated the Mycobacterium tuberculosis proteins recognized by sera from TB patient collected before and after anti-TB therapy by dynamic immunoproteomics and identified a novel immune-regulating protein 3-hydroxyacyl-l-thioester dehydratase Y (HtdY), which could induce COX-2 expression in mouse macrophages. Signaling perturbation data showed that the activation of p38, ERK 1/2 and JNK 1/2 MAPK as well as NF-κB played critical role in this immune response. Taken together, our findings indicated that mycobacterial HtdY might contribute to the persistence of the TB infection by inducing COX-2 expression through MAPK-NF-κB signaling pathway.
authors.affiliation: Department of Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Zhan-Qiang
authors.initials: ZQ
authors.lastname: Sun
authors.affiliation: Department of Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Xiang-Yan
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Shanghai Kexin Biotech Co. Ltd., Shanghai 201203, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Wuxi No. 5 People's Hospital, Wuxi, Jiangsu 214005, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Center for Pulmonary and Infectious Disease Control, The University of Texas Health Science Center, 75708 Tyler, USA.
authors.forename: Buka
authors.initials: B
authors.lastname: Samten
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200043, China.
authors.forename: Hong-Hai
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: xkguo@shsmu.edu.cn.
authors.forename: Xiao-Kui
authors.initials: XK
authors.lastname: Guo
authors.affiliation: Department of Microbiology and Parasitology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: shulinzhang@sjtu.edu.cn.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: COX-2; Dynamic immunoproteomics; HtdY; Pathway; Tuberculosis