title: Nocodazole treatment interrupted Brucella abortus invasion in RAW 264.7 cells, and successfully attenuated splenic proliferation with enhanced inflammatory response in mice.
abstract: Brucellosis is one of the most important and widespread zoonosis worldwide responsible for serious economic losses and considerable public health burden. In this study, we investigated the modulatory effect of a microtubule-inhibitor, nocodazole, on B. abortus infection in murine macrophages and in a mouse model. Nocodazole activated macrophages and directly inhibited the growth of Brucella in a dose-dependent manner. Nocodazole increased adhesion but reduced invasion and intracellular growth of Brucella in macrophages although it did not affect co-localization of Brucella with LAMP-1. In addition, nocodazole negatively affected actin polymerization, and weakly activated ERK and p38α but significantly activated JNK in non-infected cells. After subsequent infection, nocodazole weakly inhibited activation of ERK and p38α. For the in vivo tests, nocodazole -treated mice displayed elevated levels of IFN-γ, MCP-1 and IL-10 while Brucella-infected nocodazole -treated mice showed high levels of TNF, IFN-γ, MCP-1, IL-10 and IL-6 as compared to controls. Furthermore, nocodazole treatment reduced inflammation and Brucella proliferation in the spleens of mice. These findings highlight the potential use of nocodazole for the control of brucellosis although further investigations are encouraged to validate its therapeutic use in animal hosts.
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea; Department of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of the Philippines, Los Baños College, Laguna, 4031, Philippines.
authors.forename: Alisha Wehdnesday Bernardo
authors.initials: AW
authors.lastname: Reyes
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Huynh Tan
authors.initials: HT
authors.lastname: Hop
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Lauren Togonon
authors.initials: LT
authors.lastname: Arayan
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Tran Xuan Ngoc
authors.initials: TX
authors.lastname: Huy
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Wongi
authors.initials: W
authors.lastname: Min
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Hu Jang
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Hong Hee
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea; Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, 660-701, Republic of Korea. Electronic address: kimsuk@gnu.ac.kr.
authors.forename: Suk
authors.initials: S
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D058491:Bacterial Load; D002003:Brucella abortus / Q000187:drug effects* / Q000472:pathogenicity; D002006:Brucellosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology*; D010766:Phosphorylation; D000067996:RAW 264.7 Cells; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology
chemical_list: D000199:Actins; D000900:Anti-Bacterial Agents; D020928:Mitogen-Activated Protein Kinases; D015739:Nocodazole
keywords: B. abortus; Cytokine; F-actin; MAPKs; Macrophages; Nocodazole