title: Recombinant OmpA protein fragments mediate interleukin-17 regulation to prevent Escherichia coli meningitis.
abstract: BACKGROUND
  Neonates are at a higher risk for bacterial meningitis than children of other age groups. Although the mortality rates have decreased over the past few decades, neonatal meningitis is still a severe disease with high morbidity. For bacterial meningitis, antibiotic therapy is the primary choice for management. However, neurologic complications often cannot be averted; ∼40% of survivors exhibit neurological sequelae. Escherichia coli infection is the common cause of neonatal meningitis. Previously, we have demonstrated that the recombinant loop 1-3, loop 2-3, and loop 2-4 fragments of OmpA protein can protect mice from death after intracerebral E. coli infection. In this study, the protective effects of the recombinant OmpA protein fragments in E. coli intracerebral infections were investigated.
  
  
  METHODS
  The effects of E. coli intracerebral infection on cytokine and chemokine expression were determined. We also used various recombinant fragments of the OmpA protein to investigate the effects of these recombinant OmpA protein fragments on cytokine and chemokine expression.
  
  
  RESULTS
  In this study, we demonstrated that the expression of interleukin-17 and other cytokines, chemokines, inducible nitric oxide synthase, and cyclooxygenase-2 are involved in the inflammatory processes of intracerebral E. coli infection. We also demonstrated that specific recombinant OmpA protein fragments (L1-3, L2-3, L2-4, and L3) can regulate cytokine, chemokine, nitric oxide synthase, and cyclooxygenase-2 expression and, subsequently, protect mice from death caused by intracerebral infection of E. coli.
  
  
  CONCLUSIONS
  This finding indicates the potential for developing a new therapeutic approach to improve the prognosis of bacterial meningitis.
authors.affiliation: Department of Laboratory Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wen-Shyang
authors.initials: WS
authors.lastname: Hsieh
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Chih
authors.initials: CC
authors.lastname: Chang
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan; Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: wuhh@tmu.edu.tw.
authors.forename: Hsueh-Hsia
authors.initials: HH
authors.lastname: Wu
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D020381:Interleukin-17 / Q000096:biosynthesis*; D008297:Male; D020814:Meningitis, Escherichia coli / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology*; D051381:Rats
chemical_list: D001425:Bacterial Outer Membrane Proteins; D020381:Interleukin-17; D010446:Peptide Fragments; C078167:OMPA outer membrane proteins; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Escherichia coli; IL-17; NOS-2; bacterial meningitis; outer membrane protein A