title: Antimicrobial peptide LL-37 and IDR-1 ameliorate MRSA pneumonia in vivo.
abstract: BACKGROUND
  The only human cathelicidin, LL-37, and the innate defense regulator peptide IDR-1, which have been proven to have antimicrobial activity, represent essential elements of immunity. Our previous study showed that the peptide LL-37 was protective in vitro to attenuate LTA-induced inflammatory effects. Methicillin-resistant staphylococcus aureus (MRSA) causes a multitude of serious and sometimes life-threatening diseases around the globe. However, the effect of LL-37 and IDR-1 in MRSA-induced pneumonia is unknown. In the present study, we explored the potential of LL-37 and IDR-1 in ameliorating MRSA-induced pneumonia in vivo.
  
  
  METHODS
  C57BL/6 mice were randomly divided into four groups and perfused intratracheally with PBS, peptide, MRSA and MRSA plus peptide, respectively. Pulmonary tissue pathology, ELISA and quantitative RT-PCR were employed. The relative signal pathways were further explored by western blot analysis.
  
  
  RESULTS
  Pathological analysis of the lung tissue sections demonstrated that, when compared with the MRSA-treated group, both the LL-37 and IDR-1 could ameliorate the MRSA-induced pneumonia. The phosphorylation of JNK and Akt were markedly decreased in the peptide plus MRSA-treated group compared with the MRSA-treated group. Furthermore, both of them also reduced TNF-α and IL-6 production in the bronchoalveolar lavage fluid (BALF) and serum in vivo.
  
  
  CONCLUSIONS
  We report the first evidence of peptides inhibiting inflammation, decreasing the release of inflammatory cytokines and restoring pulmonary function in vivo. The antimicrobial peptide LL-37 and IDR-1 could ameliorate MRSA-induced pneumonia by exerting an anti-inflammatory property and attenuating pro-inflammatory cytokine release, thus providing support for the hypothesis that both innate and synthetic peptides could protect against MRSA in vivo.
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing Hospital of the Ministry of Health, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Hou
authors.forename: Nengwei
authors.initials: N
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Yang
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Meng
authors.forename: Ruan
authors.initials: R
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Tieying
authors.initials: T
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid; D054804:Cathelicidins / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051058:Oncogene Protein v-akt; D048031:JNK Mitogen-Activated Protein Kinases