title: Anti-inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin.
abstract: OBJECTIVE
  Transglutaminase 2 (TGase 2) expression is increased in inflammatory diseases, and TGase 2 inhibitors block these increases. We examined whether the R2 peptide inhibited the expression of TGase 2 in a mouse model of inflammatory allergic asthma.
  
  
  METHODS
  C57BL/6 mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. OVA-specific serum IgE and leukotrienes (LTs) levels were measured by enzyme-linked immunosorbent assay. Recruitment of inflammatory cells into bronchoalveolar lavage (BAL) fluid or lung tissues and goblet cell hyperplasia were assessed histologically. Airway hyperresponsiveness was determined in a barometric plethysmographic chamber. Expression of TGase 2, eosinophil major basic protein (EMBP), the adhesion molecule vascular cell adhesion molecule-1, Muc5ac and phospholipase A(2) (PLA(2) ) protein were determined by Western blot. Expression of mRNAs of Muc5ac, cytokines, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were measured by reverse transcriptase-polymerase chain reaction and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assay.
  
  
  RESULTS
  R2 peptide reduced OVA-specific IgE levels; the number of total inflammatory cells, macrophages, neutrophils, lymphocytes and eosinophils in BAL fluid and the number of goblet cells. Airway hyperresponsiveness, TGase 2 and EMBP levels, mRNA levels of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, RANTES, tumour necrosis factor-α, and MMP2/9, Muc5ac, NF-κB activity, PLA(2) activity and expressions, and LT levels in BAL cells and lung tissues were all reduced by R2 peptide. R2 peptide also restored expression of TIMP1/2.
  
  
  CONCLUSIONS
  R2 peptide reduced allergic responses by regulating NF-κB/TGase 2 activity in a mouse model of allergic asthma. This peptide may be useful in the treatment of allergic asthma.
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Bum Soo
authors.initials: BS
authors.lastname: Park
authors.forename: Gwan Ui
authors.initials: GU
authors.lastname: Hong
authors.forename: Byung Jae
authors.initials: BJ
authors.lastname: Lee
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.forename: Soo Youl
authors.initials: SY
authors.lastname: Kim
authors.forename: Jai Youl
authors.initials: JY
authors.lastname: Ro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology*; D001483:Base Sequence; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D017931:DNA Primers; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D006967:Hypersensitivity / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage*; D010455:Peptides / Q000494:pharmacology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D017931:DNA Primers; D004791:Enzyme Inhibitors; D010455:Peptides; D010047:Ovalbumin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins