Anti‐inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin

• Published in: British journal of pharmacology 2011-01, Vol.162 (1), p.210-225
• Main Authors: Kim, Dae Yong, Park, Bum Soo, Hong, Gwan Ui, Lee, Byung Jae, Park, Jung Won, Kim, Soo Youl, Ro, Jai Youl
• Format: Article
• Language: English
• Subjects: allergic asthma; Animals; Anti-Inflammatory Agents - pharmacology; Asthma; Asthma - chemically induced; Asthma - enzymology; Base Sequence; Biological and medical sciences; Blotting, Western; Bronchoalveolar Lavage Fluid; Cell adhesion & migration; Chronic obstructive pulmonary disease, asthma; Disease Models, Animal; DNA Primers; EMBP; Enzyme Inhibitors - pharmacology; Female; GTP-Binding Proteins - antagonists & inhibitors; Hypersensitivity - enzymology; inflammatory cytokines; Medical sciences; Mice; Mice, Inbred C57BL; MMP2/9; Muc5ac; Ovalbumin - administration & dosage; Peptides; Peptides - pharmacology; Pharmacology. Drug treatments; PLA2; Pneumology; Research Papers; Reverse Transcriptase Polymerase Chain Reaction; TIMP1/2; transcription factors; transglutaminase 2; Transglutaminases - antagonists & inhibitors
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2010.01033.x

BACKGROUND AND PURPOSE 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. EXPERIMENTAL APPROACH 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 A2 (PLA2) 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. KEY 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, PLA2 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. CONCLUSION AND IMPLICATIONS 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.