PMID- 20840469
OWN - NLM
STAT- MEDLINE
DCOM- 20110405
LR  - 20211203
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 162
IP  - 1
DP  - 2011 Jan
TI  - Anti-inflammatory effects of the R2 peptide, an inhibitor of transglutaminase 2, 
      in a mouse model of allergic asthma, induced by ovalbumin.
PG  - 210-25
LID - 10.1111/j.1476-5381.2010.01033.x [doi]
AB  - 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-kappaB (NF-kappaB) 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-kappaB 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-kappaB/TGase 2 activity in a mouse model 
      of allergic asthma. This peptide may be useful in the treatment of allergic 
      asthma.
CI  - (c) 2010 The Authors. British Journal of Pharmacology (c) 2010 The British 
      Pharmacological Society.
FAU - Kim, Dae Yong
AU  - Kim DY
AD  - Department of Pharmacology and Samsung Biomedical Research Institute, 
      Sungkyunkwan University School of Medicine, Suwon, Korea.
FAU - Park, Bum Soo
AU  - Park BS
FAU - Hong, Gwan Ui
AU  - Hong GU
FAU - Lee, Byung Jae
AU  - Lee BJ
FAU - Park, Jung Won
AU  - Park JW
FAU - Kim, Soo Youl
AU  - Kim SY
FAU - Ro, Jai Youl
AU  - Ro JY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (DNA Primers)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Peptides)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2)
RN  - EC 2.3.2.13 (Transglutaminases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Asthma/chemically induced/*enzymology
MH  - Base Sequence
MH  - Blotting, Western
MH  - Bronchoalveolar Lavage Fluid
MH  - DNA Primers
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/*pharmacology
MH  - Female
MH  - GTP-Binding Proteins/*antagonists & inhibitors
MH  - Hypersensitivity/*enzymology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovalbumin/*administration & dosage
MH  - Peptides/*pharmacology
MH  - Protein Glutamine gamma Glutamyltransferase 2
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transglutaminases/*antagonists & inhibitors
PMC - PMC3012417
EDAT- 2010/09/16 06:00
MHDA- 2011/04/06 06:00
PMCR- 2012/01/01
CRDT- 2010/09/16 06:00
PHST- 2010/09/16 06:00 [entrez]
PHST- 2010/09/16 06:00 [pubmed]
PHST- 2011/04/06 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.2010.01033.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2011 Jan;162(1):210-25. doi: 10.1111/j.1476-5381.2010.01033.x.