Analysis of novel disease-related genes in bronchial asthma.
Bronchial asthma is a complex disease characterized by airway inflammation involving interleukin (IL)-4 and IL-13. We have applied microarray analyses to human bronchial epithelial cultures to probe for genes regulated by these cytokines and have identified a subset of disease-relevant genes by comparison with cDNA libraries derived from normal and asthmatic bronchial biopsies. Squamous cell carcinoma antigen-1 (SCCA1) and SCCA2, the cysteine and serine protease inhibitors, respectively, showed the highest expression by IL-4 and IL-13, and particularly, SCCA1 was significantly increased in the asthmatic cDNA library. STAT6 was shown to be involved in expression of SCCA1 and SCCA2 in vitro. Furthermore, serum levels of SCCA were also elevated in asthmatic patients. Taken together, it was supposed that SCCA may play some role in the pathogenesis of bronchia asthma, and measuring its serum level may be relevant for diagnosing or monitoring the status of bronchial asthma. In a complex disorder such as asthma, this combination of in vitro and in vivo genomic approaches is a powerful discriminatory method enabling identification of novel disease-related genes and their mechanisms of regulation.
Yuyama
Noriko
N
Genox Research, Inc. Kawasaki, Japan.
Davies
Donna E
DE
Akaiwa
Mina
M
Matsui
Keiko
K
Hamasaki
Yuhei
Y
Suminami
Yoshinori
Y
Yoshida
Ning Lu
NL
Maeda
Miyako
M
Pandit
Anita
A
Lordan
James L
JL
Kamogawa
Yumiko
Y
Arima
Kazuhiko
K
Nagumo
Fumio
F
Sugimachi
Mitsuhiko
M
Berger
Ann
A
Richards
Ivan
I
Roberds
Steven L
SL
Yamashita
Tetsuji
T
Kishi
Fumio
F
Kato
Hiroshi
H
Arai
Ken-ichi
K
Ohshima
Koichi
K
Tadano
Jutaro
J
Hamasaki
Naotaka
N
Miyatake
Shoichiro
S
Sugita
Yuji
Y
Holgate
Stephen T
ST
Izuhara
Kenji
K
D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000097:blood; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020545:Respiratory Mucosa / Q000378:metabolism; D015843:Serpins
D000951:Antigens, Neoplasm; D018793:Interleukin-13; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D015847:Interleukin-4