title: RGS2-mediated intracellular Ca2+ level plays a key role in the intracellular replication of Brucella abortus within phagocytes.
abstract: BACKGROUND
  Brucella abortus can proliferate within professional and nonprofessional phagocytic host cells and thereby successfully bypass the bacteriocidal effects of phagocytes. However, the intracellular survival mechanism and factors of virulence are not fully understood.
  
  
  METHODS
  We have investigated the role of the regulator of G protein signaling 2 (RGS2), an intracellular calcium ([Ca(2+)](i)) regulator of the host cell, in the intracellular survival of B. abortus within phagocytes.
  
  
  RESULTS
  B. abortus infection markedly induced RGS2 messenger RNA expression in early phase and increased the [Ca(2+)](i) level up to 24 hours postinfection within macrophages from wild-type mice. The [Ca(2+)](i) level, however, was not influenced by B. abortus infection within macrophages from RGS2-deficient mice. Furthermore, B. abortus survival was reduced within RGS2-deficient macrophages, and hence bacterial proliferation was inhibited in RGS2-deficient mice. Moreover, treatment with the Ca(2+) chelator ethylenediaminetetraacetic acid (EDTA) or 1,2-bis-(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and the L-type Ca(2+) channel-blocking agent nifedipine or genistein also showed a reduced intracellular replication of B. abortus within macrophages.
  
  
  CONCLUSIONS
  These results indicate that B. abortus infection induces host RGS2 expression and that up-regulation of [Ca(2+)](i) levels is an essential factor for the intracellular survival of B. abortus within phagocytes.
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju, Japan.
authors.forename: Dong Hyeok
authors.initials: DH
authors.lastname: Kim
authors.forename: Jeong Ju
authors.initials: JJ
authors.lastname: Lim
authors.forename: Jin Ju
authors.initials: JJ
authors.lastname: Lee
authors.forename: Dae Geun
authors.initials: DG
authors.lastname: Kim
authors.forename: Hu Jang
authors.initials: HJ
authors.lastname: Lee
authors.forename: Wongi
authors.initials: W
authors.lastname: Min
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Hong Hee
authors.initials: HH
authors.lastname: Chang
authors.forename: Mehari
authors.initials: M
authors.lastname: Endale
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.forename: Masahisa
authors.initials: M
authors.lastname: Watarai
authors.forename: Suk
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D002003:Brucella abortus / Q000254:growth & development* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism*; D002470:Cell Survival; D015169:Colony Count, Microbial; D003600:Cytosol / Q000737:chemistry / Q000382:microbiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology*; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000382:microbiology / Q000473:pathology
chemical_list: D002413:Cations, Divalent; D020710:RGS Proteins; C105345:Rgs2 protein, mouse; D002118:Calcium