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

作者：Kim Dae Yong; Park Bum Soo; Hong Gwan Ui; Lee Byung Jae; Park Jung Won; Kim Soo Youl; Ro Jai Youl^*

来源：British Journal of Pharmacology, 2011, 162(1): 210-225.

DOI：10.1111/j.1476-5381.2010.01033.x

• transglutaminase 2
• allergic asthma
• EMBP
• Muc5ac
• MMP2
• 9
• TIMP1
• 2
• inflammatory cytokines
• transcription factors
• PLA(2)

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-kappa B (NF-kappa B) 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-alpha, and MMP2/9, Muc5ac, NF-kappa B 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-kappa B/TGase 2 activity in a mouse model of allergic asthma. This peptide may be useful in the treatment of allergic asthma.

• 出版日期2011-1