Identification of a novel cytokine, ML-1, and its expression in subjects with asthma

被引:155
作者
Kawaguchi, M
Onuchic, LF
Li, XD
Essayan, DM
Schroeder, J
Xiao, HQ
Liu, MC
Krishnaswamy, G
Germino, G
Huang, SK
机构
[1] Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA
[3] Univ Sao Paulo, Sch Med, Div Nephrol, BR-05508900 Sao Paulo, Brazil
[4] E Tennessee State Univ, Dept Med, Johnson City, TN 37614 USA
关键词
D O I
10.4049/jimmunol.167.8.4430
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A novel gene, designated ML-1, was identified front a human genomic DNA clone and human T cell cDNA sequences. The second exon of ML-1 gene shares significant sequence identity with the gene encoding IL-17 (IL-17). ML-1 gene expression was upregulated in activated PBMCs, CD4(+) T cells, allergen-specific Th0, Th1, and Th2 clones, activated basophils, and mast cells. Increased expression of the ML-1 gene, but not IL-17, was seen following allergen challenge in four asthmatic subjects, suggesting its role in allergic inflammatory responses. ML-1 from transiently transfected COS-7 cells was able to induce gene expression and protein production for IL-6 and IL-8 (at 10 ng/ml of ML-1: for IL-6, 599.6 +/- 19.1 pg/ml; for IL-8, 1724.2 +/- 132.9 pg/ml; and at 100 ng/ml of ML-1: for IL-6, 1005.3 +/- 55.6 pg/ml; for IL-8, 4371.4 +/- 280.5 pg/ml; p < 0.05 for both doses vs baseline) in primary bronchial epithelial (PBE) cells. Furthermore, increased expression of ICAM-1 was found in ML-1-stimulated PBE cells (mean fluorescence intensity (MFI) = 31.42 +/- 4.39 vs baseline, MFI = 12.26 +/- 1.77, p < 0.05), a functional feature distinct from IL-17 (MFI = 11.07 +/- 1.22). This effect was not inhibited by a saturating amount of IL-17. These findings demonstrate that ML-1 is a novel cytokine with a distinct function, and suggest a different receptor for ML-1 on PBE cells.
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收藏
页码:4430 / 4435
页数:6
相关论文
共 26 条
[1]  
Aarvak T, 1999, J IMMUNOL, V162, P1246
[2]   Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-γ- and interleukin-4-induced activation of human keratinocytes [J].
Albanesi, C ;
Scarponi, CS ;
Cavani, A ;
Federici, M ;
Nasorri, F ;
Girolomoni, G .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 115 (01) :81-87
[3]   Interleukin-17 up-regulation of nitric oxide production in human osteoarthritis cartilage [J].
Attur, MG ;
Patel, RN ;
Abramson, SB ;
Amin, AR .
ARTHRITIS AND RHEUMATISM, 1997, 40 (06) :1050-1053
[4]   EXPRESSION OF ENDOTHELIAL AND LEUKOCYTE ADHESION MOLECULES INTERCELLULAR-ADHESION MOLECULE-1, E-SELECTIN, AND VASCULAR CELL-ADHESION MOLECULE-1 IN THE BRONCHIAL-MUCOSA IN STEADY-STATE AND ALLERGEN-INDUCED ASTHMA [J].
BENTLEY, AM ;
DURHAM, SR ;
ROBINSON, DS ;
MENZ, G ;
STORZ, C ;
CROMWELL, O ;
KAY, AB ;
WARDLAW, AJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1993, 92 (06) :857-868
[5]   Regulation of granulocyte colony-stimulating factor gene expression by interleukin-17 [J].
Cai, XY ;
Gommoll, CP ;
Justice, L ;
Narula, SK ;
Fine, JS .
IMMUNOLOGY LETTERS, 1998, 62 (01) :51-58
[6]  
CROMWELL O, 1992, IMMUNOLOGY, V77, P330
[7]   Clonal diversity of IL-4 and IL-13 expression in human allergen-specific T lymphocytes [J].
Essayan, DM ;
Han, WF ;
Li, XM ;
Xiao, HQ ;
KleineTebbe, J ;
Huang, SK .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1996, 98 (06) :1035-1044
[8]   PROMINENT NEUTROPHILIC INFLAMMATION IN SPUTUM FROM SUBJECTS WITH ASTHMA EXACERBATION [J].
FAHY, JV ;
KIM, KW ;
LIU, J ;
BOUSHEY, HA .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1995, 95 (04) :843-852
[9]   T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J].
Fossiez, F ;
Djossou, O ;
Chomarat, P ;
FloresRomo, L ;
AitYahia, S ;
Maat, C ;
Pin, JJ ;
Garrone, P ;
Garcia, E ;
Saeland, S ;
Blanchard, D ;
Gaillard, C ;
DasMahapatra, B ;
Rouvier, E ;
Golstein, P ;
Banchereau, J ;
Lebecque, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (06) :2593-2603
[10]  
HUANG SK, 1995, J IMMUNOL, V155, P2688