PMID- 14604971
OWN - NLM
STAT- MEDLINE
DCOM- 20040415
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 6
DP  - 2004 Mar 15
TI  - Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine 
      expression in mice.
PG  - 2196-204
AB  - Asthma is one of the most common diseases and is characterized by airway 
      obstruction, airway inflammation, and increased airway responsiveness. 
      Glucocorticoids are very effective in treatment, but their long-term use is 
      associated with several side effects, so that new anti-inflammatory drugs are in 
      development. Activated protein C (APC) is a serine protease with potent 
      anti-inflammatory effects. This study evaluated the effect of inhaled APC on 
      airway inflammation and hyperresponsiveness in a murine asthma model. Asthma was 
      induced in BALB/c mice by exposure to chicken egg ovalbumin (OVA), and the effect 
      of inhaled APC was assessed by administering prior to OVA exposure. Inhalation of 
      APC significantly inhibited the expression of T helper 2 (Th2) cytokines, 
      immunoglobulin E (IgE), eosinophilic inflammation, and hyperresponsiveness. APC 
      also significantly suppressed the expression of Th2 cytokines and IgE from 
      lymphocytes isolated from OVA-sensitized/challenged animals. In addition, binding 
      of signal transducer and activator of transcription 6 (STAT6) and nuclear factor 
      kappa B (NF-kappa B) oligonucleotides to lung nuclear proteins was significantly 
      reduced in mice treated with inhaled APC. In brief, the exogenous supplementation 
      of APC inhibits the immunologic and inflammatory responses induced by Th2 
      cytokines in a mouse model of asthma and may represent a novel anti-inflammatory 
      treatment.
FAU - Yuda, Hisamichi
AU  - Yuda H
AD  - Third Department of Internal Medicine, Mie University School of Medicine, Tsu, 
      Mie 514 8507, Japan.
FAU - Adachi, Yukihiko
AU  - Adachi Y
FAU - Taguchi, Osamu
AU  - Taguchi O
FAU - Gabazza, Esteban C
AU  - Gabazza EC
FAU - Hataji, Osamu
AU  - Hataji O
FAU - Fujimoto, Hajime
AU  - Fujimoto H
FAU - Tamaki, Shigenori
AU  - Tamaki S
FAU - Nishikubo, Kimiaki
AU  - Nishikubo K
FAU - Fukudome, Kenji
AU  - Fukudome K
FAU - D'Alessandro-Gabazza, Corina N
AU  - D'Alessandro-Gabazza CN
FAU - Maruyama, Junko
AU  - Maruyama J
FAU - Izumizaki, Masahiko
AU  - Izumizaki M
FAU - Iwase, Michiko
AU  - Iwase M
FAU - Homma, Ikuo
AU  - Homma I
FAU - Inoue, Ryo
AU  - Inoue R
FAU - Kamada, Haruhiko
AU  - Kamada H
FAU - Hayashi, Tatsuya
AU  - Hayashi T
FAU - Kasper, Michael
AU  - Kasper M
FAU - Lambrecht, Bart N
AU  - Lambrecht BN
FAU - Barnes, Peter J
AU  - Barnes PJ
FAU - Suzuki, Koji
AU  - Suzuki K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20031106
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies)
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Cytokines)
RN  - 0 (Endothelial Protein C Receptor)
RN  - 0 (Endothelins)
RN  - 0 (Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (PROCR protein, human)
RN  - 0 (Protein C)
RN  - 0 (Receptor, PAR-1)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
RN  - 0 (Stat6 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (leukocyte procoagulant activity)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Antibodies
MH  - Antigens, CD
MH  - Asthma/*drug therapy/immunology/metabolism
MH  - Biomarkers
MH  - Blood Coagulation Factors/immunology
MH  - Bronchial Hyperreactivity/*drug therapy/immunology/metabolism
MH  - Cytokines/metabolism
MH  - Dinoprostone/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Protein C Receptor
MH  - Endothelins/genetics/immunology
MH  - Eosinophils/immunology
MH  - Female
MH  - Glycoproteins
MH  - HeLa Cells
MH  - Humans
MH  - Hypersensitivity/drug therapy/immunology/metabolism
MH  - Immunoglobulin E/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Ovalbumin/immunology
MH  - Protein C/*pharmacology
MH  - Receptor, PAR-1/antagonists & inhibitors
MH  - Receptors, Cell Surface
MH  - STAT6 Transcription Factor
MH  - Specific Pathogen-Free Organisms
MH  - Th2 Cells/drug effects/*immunology
MH  - Thrombin/metabolism
MH  - Trans-Activators/metabolism
MH  - U937 Cells
EDAT- 2003/11/08 05:00
MHDA- 2004/04/16 05:00
CRDT- 2003/11/08 05:00
PHST- 2003/11/08 05:00 [pubmed]
PHST- 2004/04/16 05:00 [medline]
PHST- 2003/11/08 05:00 [entrez]
AID - S0006-4971(20)50014-1 [pii]
AID - 10.1182/blood-2003-06-1980 [doi]
PST - ppublish
SO  - Blood. 2004 Mar 15;103(6):2196-204. doi: 10.1182/blood-2003-06-1980. Epub 2003 
      Nov 6.