PMID- 17941913
OWN - NLM
STAT- MEDLINE
DCOM- 20081006
LR  - 20071121
IS  - 1365-2222 (Electronic)
IS  - 0954-7894 (Linking)
VI  - 37
IP  - 12
DP  - 2007 Dec
TI  - Neurokinin-1 receptor activation induces reactive oxygen species and epithelial 
      damage in allergic airway inflammation.
PG  - 1788-97
AB  - BACKGROUND: An induction of reactive oxygen species (ROS) is characteristic for 
      inflammation but the exact pathways have not been identified for allergic airway 
      diseases so far. OBJECTIVE: The aim of this study was to characterize the role of 
      the tachykinin NK-1 receptor on ROS production during allergen challenge and 
      subsequent inflammation and remodelling. METHODS: Precision-cut lung slices of 
      ovalbumin (OVA)-sensitized mice were cultivated and ROS-generation in response to 
      OVA challenge (10 microg/mL) was examined by the 
      2',7'-dichloroflourescein-diacetate method. Long-term ROS effects on epithelial 
      proliferation were investigated by 5-bromo-2'-deoxyuridine incorporation (72 h). 
      In vivo, the results were validated in OVA-sensitized animals which were treated 
      intra-nasally with either placebo, the tachykinin neurokinin 1 (NK-1) receptor 
      antagonist SR 140333 or the anti-oxidant N-acetylcystein (NAC) before allergen 
      challenge. Inflammatory infiltration and remodelling were assessed 48 h after 
      allergen challenge. RESULTS: ROS generation was increased by 3.7-fold, which was 
      inhibited by SR 140333. [Sar(9),Met(11)(O(2))]-Substance P (5 nM) caused a 
      tachykinin NK-1 receptor-dependent fourfold increase in ROS generation. 
      Epithelial proliferation was decreased by 68% by incubation with 
      [Sar(9),Met(11)(O(2))]-SP over 72 h. In-vivo, treatment with SR 140333 and NAC 
      reduced epithelial damage (91.4% and 76.8% vs. placebo, respectively, P<0.01) and 
      goblet cell hyperplasia (67.4% and 50.1% vs. placebo, respectively, P<0.05), and 
      decreased inflammatory cell influx (65.3% and 45.3% vs. placebo, respectively, 
      P<0.01). CONCLUSION: Allergen challenge induces ROS in a tachykinin NK-1 
      receptor-dependent manner. Inhibition of the tachykinin NK-1 receptor reduces 
      epithelial damage and subsequent remodelling in vivo. Therefore, patients may 
      possibly benefit from treatment regime that includes radical scavengers or 
      tachykinin NK-1 receptor antagonists.
FAU - Springer, J
AU  - Springer J
AD  - Department of Cardiology, Division of Applied Cachexia Research, Charite Medical 
      School, Berlin, Germany. jochen.springer@charite.de
FAU - Groneberg, D A
AU  - Groneberg DA
FAU - Dinh, Q T
AU  - Dinh QT
FAU - Quarcoo, D
AU  - Quarcoo D
FAU - Hamelmann, E
AU  - Hamelmann E
FAU - Braun-Dullaeus, R C
AU  - Braun-Dullaeus RC
FAU - Geppetti, P
AU  - Geppetti P
FAU - Anker, S D
AU  - Anker SD
FAU - Fischer, A
AU  - Fischer A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071016
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Neurokinin-1)
SB  - IM
MH  - Animals
MH  - Cell Cycle Proteins/metabolism
MH  - Epithelial Cells/*metabolism
MH  - Hypersensitivity/*metabolism/*pathology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Pneumonia/*metabolism/*pathology
MH  - Reactive Oxygen Species/*metabolism
MH  - Receptors, Neurokinin-1/*metabolism
EDAT- 2007/10/19 09:00
MHDA- 2008/10/07 09:00
CRDT- 2007/10/19 09:00
PHST- 2007/10/19 09:00 [pubmed]
PHST- 2008/10/07 09:00 [medline]
PHST- 2007/10/19 09:00 [entrez]
AID - CEA2851 [pii]
AID - 10.1111/j.1365-2222.2007.02851.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 2007 Dec;37(12):1788-97. doi: 10.1111/j.1365-2222.2007.02851.x. 
      Epub 2007 Oct 16.