Regulation of 15-lipoxygenase expression in lung epithelial cells by interleukin-4

被引:84
作者
Brinckmann, R
Topp, MS
Zalan, I
Heydeck, D
Ludwig, P
Kuhn, H
Berdel, WE
Habenicht, AJR
机构
[1] HUMBOLDT UNIV BERLIN, CLIN CHARITE, INST BIOCHEM, D-10115 BERLIN, GERMANY
[2] FREE UNIV BERLIN, KLINIKUM BENJAMIN FRANKLIN, DEPT INTERNAL MED, D-12200 BERLIN, GERMANY
[3] UNIV HEIDELBERG, DIV ENDOCRINOL & METAB, CLIN INTERNAL MED, D-69115 HEIDELBERG, GERMANY
关键词
D O I
10.1042/bj3180305
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
We have studied the expression of the 15-lipoxygenase gene in various permanent mammalian cell lines in response to interleukins-il and -13, and found that none of the cell lines tested expressed 5-, 12- or 15-lipoxygenase when cultured under standard conditions. However, when the lung carcinoma cell line A549 was maintained in the presence of either interleukin for 24 h or more, we observed a major induction of 15-lipoxygenase, as indicated by quantification of 15-lipoxygenase mRNA, by immunohistochemistry, by immunoblot analysis and by enzyme activity assays. This effect was 15-lipoxygenase-specific, since expression of 5- and 12-lipoxygenases remained undetectable. The time course of interleukin-4 treatment indicated maximal accumulation of both 15-lipoxygenase mRNA and functional protein after 48 h. Binding studies revealed that A549 cells express about 2100 high-affinity interleukin-4 binding sites per cell. The interleukin-4 mutant Y124D, which is capable of binding to the interleukin-4 receptor but is unable to trigger receptor activation, counteracted the effect of the wild-type cytokine. Other cell lines, including several epithelial cells and various monocytic cell lines expressing comparable numbers of interleukin-4 receptors, did not express 15-lipoxygenase when stimulated with interleukin-4. These data indicate that A549 cells selectively express 15-lipoxygenase when stimulated with interleukins-4 and -13. The activation of the interleukin-4/13 receptor(s) appears to be mandatory, but not sufficient, for 15-lipoxygenase gene expression.
引用
收藏
页码:305 / 312
页数:8
相关论文
共 56 条
  • [1] ARRUDA S, 1992, J IMMUNOL, V149, P1258
  • [2] BECKMANN MP, 1992, CHEM IMMUNOL, V51, P107
  • [3] OXYGENATION OF LIPOPROTEINS BY MAMMALIAN LIPOXYGENASES
    BELKNER, J
    WIESNER, R
    RATHMAN, J
    BARNETT, J
    SIGAL, E
    KUHN, H
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 213 (01): : 251 - 261
  • [4] SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION
    CHOMCZYNSKI, P
    SACCHI, N
    [J]. ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) : 156 - 159
  • [5] SPECIFIC INFLAMMATORY CYTOKINES REGULATE THE EXPRESSION OF HUMAN MONOCYTE 15-LIPOXYGENASE
    CONRAD, DJ
    KUHN, H
    MULKINS, M
    HIGHLAND, E
    SIGAL, E
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (01) : 217 - 221
  • [6] CONRAD DJ, 1994, 9 INT C PROST REL CO, P39
  • [7] ANALYSIS OF CYTOKINE MESSENGER-RNA AND DNA - DETECTION AND QUANTITATION BY COMPETITIVE POLYMERASE CHAIN-REACTION
    GILLILAND, G
    PERRIN, S
    BLANCHARD, K
    BUNN, HF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (07) : 2725 - 2729
  • [8] UPTAKE, RELEASE AND NOVEL SPECIES-DEPENDENT OXYGENATION OF ARACHIDONIC-ACID IN HUMAN AND ANIMAL AIRWAY EPITHELIAL-CELLS
    HOLTZMAN, MJ
    HANSBROUGH, JR
    ROSEN, GD
    TURK, J
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1988, 963 (03) : 401 - 413
  • [9] AN INTERLEUKIN-4-INDUCED TRANSCRIPTION FACTOR - IL-4 STAT
    HOU, JZ
    SCHINDLER, U
    HENZEL, WJ
    HO, TC
    BRASSEUR, M
    MCKNIGHT, SL
    [J]. SCIENCE, 1994, 265 (5179) : 1701 - 1706
  • [10] 15-LIPOXYGENASE EXPRESSION IN SMOOTH-MUSCLE CELLS FROM ATHEROSCLEROTIC RABBIT AORTAS
    HUGOU, I
    BLIN, P
    HENRI, J
    DARET, D
    LARRUE, J
    [J]. ATHEROSCLEROSIS, 1995, 113 (02) : 189 - 195