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

Dae Yong Kim, Bum Soo Park, Gwan Ui Hong, Byung Jae Lee, Jungwon Park, Soo Youl Kim, Jai Youl Ro

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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 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. 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, 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. 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.

Original languageEnglish
Pages (from-to)210-225
Number of pages16
JournalBritish Journal of Pharmacology
Volume162
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

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Ovalbumin
Anti-Inflammatory Agents
Asthma
Peptides
Eosinophil Major Basic Protein
Goblet Cells
Leukotrienes
Phospholipases A
Bronchoalveolar Lavage Fluid
Immunoglobulin E
Tissue Inhibitor of Metalloproteinases
Chemokine CCL5
Lung
Messenger RNA
Matrix Metalloproteinase Inhibitors
Interleukin-13
Vascular Cell Adhesion Molecule-1
Interleukin-5
Electrophoretic Mobility Shift Assay
Bronchoalveolar Lavage

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Kim, Dae Yong ; Park, Bum Soo ; Hong, Gwan Ui ; Lee, Byung Jae ; Park, Jungwon ; Kim, Soo Youl ; Ro, Jai Youl. / Anti-inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin. In: British Journal of Pharmacology. 2011 ; Vol. 162, No. 1. pp. 210-225.
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abstract = "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 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. 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, 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. 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.",
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Anti-inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, in a mouse model of allergic asthma, induced by ovalbumin. / Kim, Dae Yong; Park, Bum Soo; Hong, Gwan Ui; Lee, Byung Jae; Park, Jungwon; Kim, Soo Youl; Ro, Jai Youl.

In: British Journal of Pharmacology, Vol. 162, No. 1, 01.01.2011, p. 210-225.

Research output: Contribution to journalArticle

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AU - Kim, Dae Yong

AU - Park, Bum Soo

AU - Hong, Gwan Ui

AU - Lee, Byung Jae

AU - Park, Jungwon

AU - Kim, Soo Youl

AU - Ro, Jai Youl

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N2 - 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 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. 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, 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. 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.

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