title: Analysis of nucleotide-binding oligomerization domain proteins in a murine model of pneumococcal meningitis.
abstract: BACKGROUND
  The innate immune system recognizes pathogens via its pattern recognition receptors. The objective of this study was to investigate the role of the nucleotide-binding oligomerization domain (NOD) proteins, a family of the novel bacterial pattern recognition receptors, in host responses to the gram-positive bacteria Streptococcus pneumoniae.
  
  
  METHODS
  Sprague-Dawley rats were infected via intracisternal injections of viable S. pneumoniae, and rats in the control group were injected with sterile saline. After infection, real-time PCR was performed to determine the presence of mRNAs encoding NOD1 and NOD2. Quantitative analyses of the NOD1, NOD2 and NF-kB proteins were also performed western blotting following challenge infections with viable S. pneumoniae. The TNF-α and IL-6 levels in brain homogenates were evaluated using enzyme-linked immunosorbent assays (ELISAs).
  
  
  RESULTS
  The results revealed up-regulations of the mRNA and protein levels of NOD2 within the CNS of rats with S. pneumoniae meningitis. Moreover, the activation of NF-κB in the brain tissues following infection with live S. pneumoniae was also significantly increased, which indicates that NOD2 mediated NF-κB activation in experimental pneumococcal meningitis. Similarly, TNF-α and IL-6 levels were increased in the brain following in vivo S. pneumoniae administration.
  
  
  CONCLUSIONS
  These results suggest that NOD2 is involved in the host response to the gram-positive bacteria S. pneumoniae in the CNS and that NOD2 might play an important role in the initiation and/or progression of CNS inflammation associated with pneumococcal meningitis.
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, No. 107 Wen Hua Xi Road, Jinan, People's Republic of China. liuxinjie@sdu.edu.cn.|Brain Science Research Institute, Shandong University, No. 107 Wen Hua Xi Road, Jinan, People's Republic of China. liuxinjie@sdu.edu.cn.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Provincial Hospital Affiliated to Shandong University, No. 4 Duan Xing Xi Road, Jinan, People's Republic of China. hanqizheng@163.com.
authors.forename: Qizheng
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Ultrasonic Diagnosis, Jinan Maternity and Children Care Hospital, Jian Guo Xiao Jing San Road, Jinan, People's Republic of China. Ljhjshchu@163.com.
authors.forename: Junhong
authors.initials: J
authors.lastname: Leng
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000378:metabolism; D008586:Meningitis, Pneumococcal / Q000378:metabolism / Q000382:microbiology*; D016328:NF-kappa B / Q000378:metabolism; D053472:Nod Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; C512493:NOD2 protein, rat; D053472:Nod Signaling Adaptor Proteins; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha