Expression of the Ym2 lectin-binding protein is dependent on interleukin (IL)-4 and IL-13 signal transduction - Identification of a novel allergy-associated protein

被引:133
作者
Webb, DC
McKenzie, ANJ
Foster, PS [1 ]
机构
[1] Australian Natl Univ, John Curtin Sch Med Res, Div Biochem & Mol Biol, Canberra, ACT 2601, Australia
[2] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
关键词
D O I
10.1074/jbc.M106223200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Asthma pathophysiology is intimately regulated by CD4(+) Th2 lymphocytes and the cytokines interleukin (IL)-4 and IL-13. However, the mechanisms by which these cytokines promote disease have not been fully elucidated. In order to identify novel molecular mediators of allergy, a comparison was made of the bronchoalveolar lavage, which demonstrated that the Ym2 protein was abundantly up-regulated in the lung during the development of allergy. Low levels of the Ym1 isomer were also detected. Importantly, neither Ym1 nor Ym2 has been characterized previously in the context of allergic pulmonary inflammation. Western immunoblot showed that enhanced expression of these proteins was dependent on CD4(+) T cells and IL-4 or IL-13 signaling via the IL-4R alpha subunit. In addition, intratracheal instillation of IL-13 into naive mice was sufficient to induce expression. Ym1 is homologous to eosinophil chemotactic factor L. However, only weak eosinophil chemotaxis was observed in response to Ym protein in both in vitro and in vivo assays. By contrast, the homology of Ym1 and Ym2 to proteins associated with tissue remodeling, together with the previous findings that Ym1 is homologous to chitinase and binds heparin sulfate and GlcN oligomers (chitobiose, chitotriose, and chitotetraose), strongly suggests these proteins play an important role in airway wall remodeling in the allergic lung.
引用
收藏
页码:41969 / 41976
页数:8
相关论文
共 43 条
[21]   Consequences of long-term inflammation - Airway remodeling [J].
Homer, RJ ;
Elias, JA .
CLINICS IN CHEST MEDICINE, 2000, 21 (02) :331-+
[22]   Genetic characterization of the murine Ym1 gene and identification of a cluster of highly homologous genes [J].
Jin, HM ;
Copeland, NG ;
Gilbert, DJ ;
Jenkins, NA ;
Kirkpatrick, RB ;
Rosenberg, M .
GENOMICS, 1998, 54 (02) :316-322
[23]   DISRUPTION OF THE MURINE IL-4 GENE BLOCKS TH2 CYTOKINE RESPONSES [J].
KOPF, M ;
LEGROS, G ;
BACHMANN, M ;
LAMERS, MC ;
BLUETHMANN, H ;
KOHLER, G .
NATURE, 1993, 362 (6417) :245-248
[24]   Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells [J].
Malinda, KM ;
Ponce, L ;
Kleinman, HK ;
Shackelton, LM ;
Millis, AJT .
EXPERIMENTAL CELL RESEARCH, 1999, 250 (01) :168-173
[25]   Impaired development of Th2 cells in IL-13-deficient mice [J].
McKenzie, GJ ;
Emson, CL ;
Bell, SE ;
Anderson, S ;
Fallon, P ;
Zurawski, G ;
Murray, R ;
Grencis, R ;
McKenzie, ANJ .
IMMUNITY, 1998, 9 (03) :423-432
[26]  
Murata T, 1998, INT J MOL MED, V1, P551
[27]   An interleukin 4 (IL-4)-independent pathway for CD4(+) T cell IL-4 production is revealed in IL-4 receptor-deficient mice [J].
NobenTrauth, N ;
Shultz, LD ;
Brombacher, F ;
Urban, JF ;
Gu, H ;
Paul, WE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10838-10843
[28]   Production of eosinophil chemotactic factor by CD8+ T-cells in Toxocara canis-infected mice [J].
Owhashi M. .
Parasitology Research, 1997, 84 (2) :136-138
[29]   EOSINOPHIL CHEMOTACTIC LYMPHOKINE PRODUCED BY SPLEEN-CELLS OF SCHISTOSOMA-JAPONICUM-INFECTED MICE .3. ISOLATION AND CHARACTERIZATION OF 2 DISTINCTIVE EOSINOPHIL CHEMOTACTIC LYMPHOKINES DIRECTED AGAINST DIFFERENT MATURATION STAGES OF EOSINOPHILS [J].
OWHASHI, M ;
NAWA, Y .
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 1987, 84 (02) :185-189
[30]   Identification of a novel eosinophil chemotactic cytokine (ECF-L) as a chitinase family protein [J].
Owhashi, M ;
Arita, H ;
Hayai, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (02) :1279-1286