title: BaeR protein acts as an activator of nuclear factor-kappa B and Janus kinase 2 to induce inflammation in murine cell lines.
abstract: BaeR, a response regulator protein, takes part in multidrug efflux, bacterial virulence activity, and other biological functions. Recently, BaeR was shown to induce inflammatory responses by activating the mitogen-activated protein kinases (MAPKs). In this study, we investigated additional pathways used by BaeR to induce an inflammatory response. BaeR protein was purified from Salmonella enterica Paratyphi A and subcloned into a pPosKJ expression vector. RAW 264.7 cells were treated with BaeR, and RNA was extracted by TRIzol reagent for RT-PCR. Cytokine gene expression was analyzed by using the comparative cycle threshold method, while western blotting and ELISA were used to assess protein expression. We confirmed that BaeR activates nuclear factor-kappa B (NF-κB), thereby inducing an inflammatory response and increases the production of interleukins (IL-)1β and IL-6. During this process, the Janus kinase 2 (JAK2)-STAT1 signaling pathway was activated, resulting in an increase in the release of interferons I and II. Additionally, COX-2 was activated and its expression increased with time. In conclusion, BaeR induced an inflammatory response through activation of NF-κB in addition to the MAPKs. Furthermore, activation of the JAK2-STAT1 pathway and COX-2 facilitated the cytokine binding activity, suggesting an additional role for BaeR in the modulation of the immune system of the host and the virulence activity of the pathogen.
authors.affiliation: a Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: a Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Biruk Tesfaye
authors.initials: BT
authors.lastname: Birhanu
authors.affiliation: b COPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors.forename: Elias Gebru
authors.initials: EG
authors.lastname: Awji
authors.affiliation: c Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, KRIBB, Daejeon 305-806, Republic of Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: d Cleanbio Research Institute, Daejeon 301-212, Korea.
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: e Center for Nutraceutical and Pharmaceutical Materials, Division of Bioscience and Bioinformatics, Science campus, Myongji University, 449-728 Yongin, Gyeonggi, Republic of Korea.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
authors.affiliation: a Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Seung-Chun
authors.initials: SC
authors.lastname: Park
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; C000613133:BaeR protein, Salmonella enterica; D016207:Cytokines; D052002:NF-kappa B p50 Subunit; C073701:Nfkb1 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: BaeR; JAK2; NF-κB; Salmonella enterica Paratyphi A; nitric oxide; oxyde nitrique