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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.

Authors: Kim, DY  Park, BS  Hong, GU  Lee, BJ  Park, JW  Kim, SY  Ro, JY 
Citation: Kim DY, etal., Br J Pharmacol. 2010 Sep 14. doi: 10.1111/j.1476-5381.2010.01033.x.
Pubmed: (View Article at PubMed) PMID:20840469
DOI: Full-text: 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 ELISA. 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 VCAM-1, Muc5ac and phospholipase A(2) (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 RT-PCR, and nuclear factor-kappaB (NF-kappaB) by EMSA. 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, TNF-alpha, and MMP2/9, Muc5ac, NF-kappaB 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-kappaB/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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CRRD Object Information
CRRD ID: 4143265
Created: 2010-09-21
Species: All species
Last Modified: 2010-09-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.