Orbital fibroblast interleukin-6 gene expression and immunomodulation

被引:4
作者
Burnstine, MA [1 ]
Elner, SG [1 ]
Strieter, RM [1 ]
Kunkel, SL [1 ]
Elner, VM [1 ]
机构
[1] Univ Michigan, Sch Med, Dept Ophthalmol, WK Kellogg Eye Ctr, Ann Arbor, MI USA
关键词
D O I
10.1097/00002341-199909000-00002
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: Orbital inflammation is common, but the mechanisms underlying leukocytic infiltration of orbital tissue are poorly understood. We studied human orbital fibroblast (OF) interleukin-6 (IL-6) gene expression in response to proinflammatory stimuli and the effects of dexamethasone (DEX) and cyclosporin A (CSA) on cytokine-stimulated OF IL-6 gene expression. Methods: Cultured OFs were left unstimulated or incubated with varying concentrations of lipopolysaccharide (LPS), or recombinant (r) interleukin-1-beta (rIL-1 beta), tumor necrosis factor-alpha (rTNF-alpha), or interferon-gamma (rIFN-gamma) for 2, 4, 8, or 24 hours. OFs were also incubated with rIL-1 beta (0.2, 2.0, 20 ng/ml) alone or in the presence of DEX (10(-8), 10(-7), 10(-6) mol/l) or CSA (3, 30, 300 ng/ml) for 8 hours to determine the effects of these immunomodulating drugs on IL-6 expression. Northern blot analyses were performed to determine OF IL-6 mRNA expression in response to varying concentrations of these agents. Experiments were repeated four times on different cell lines. Results: OFs lacked constitutive IL-6 gene expression. Substantial time- and dose-dependent increases in steady-state IL-6 mRNA expression occurred by 4 hours of LPS or cytokine stimulation (rIL-1 beta>rTNF-alpha>LPS>rIFN-gamma), peaked at 8 hours, and were maintained at 24 hours. DEX caused dose-dependent inhibition of IL-1-induced IL-6 mRNA expression, while CSA potentiated IL-1-induced OF IL-6 mRNA expression. Conclusions: OFs express IL-6 mRNA in response to proinflammatory stimuli. DEX is a potent inhibitor of OF IL-6 mRNA while CSA increases IL-1-induced OF IL-6 gene expression. These observations may in part explain the lack of CSA effectiveness in human orbital diseases that respond to corticosteroids.
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收藏
页码:306 / 311
页数:6
相关论文
共 44 条
  • [1] BIOLOGY OF MULTIFUNCTIONAL CYTOKINES - IL-6 AND RELATED MOLECULES (IL-1 AND TNF)
    AKIRA, S
    HIRANO, T
    TAGA, T
    KISHIMOTO, T
    [J]. FASEB JOURNAL, 1990, 4 (11) : 2860 - 2867
  • [2] AMANO Y, 1993, MOL PHARMACOL, V43, P176
  • [3] BAGGIOLINI M, 1994, ADV IMMUNOL, V55, P97
  • [4] BAUER J, 1988, BLOOD, V72, P1134
  • [5] Orbital fibroblast chemokine modulation: effects of dexamethasone and cyclosporin A
    Burnstine, MA
    Elner, SG
    Elner, VM
    [J]. BRITISH JOURNAL OF OPHTHALMOLOGY, 1998, 82 (03) : 318 - 322
  • [6] ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE
    CHIRGWIN, JM
    PRZYBYLA, AE
    MACDONALD, RJ
    RUTTER, WJ
    [J]. BIOCHEMISTRY, 1979, 18 (24) : 5294 - 5299
  • [7] CICCO NA, 1990, BLOOD, V75, P2049
  • [8] ANALYSIS OF IL-6 LEVELS IN HUMAN VITREOUS FLUID OBTAINED FROM UVEITIS PATIENTS, PATIENTS WITH PROLIFERATIVE INTRAOCULAR DISORDERS AND EYE BANK EYES
    DEBOER, JH
    VANHAREN, MAC
    DEVRIESKNOPPERT, WAEJ
    BAARSMA, GS
    DEJONG, PVTM
    POSTEMA, FJ
    RADEMAKERS, AJJM
    KIJLSTRA, A
    [J]. CURRENT EYE RESEARCH, 1992, 11 : 181 - 186
  • [9] DEVOS AF, 1994, INVEST OPHTH VIS SCI, V35, P1100
  • [10] ELIAS JA, 1990, J IMMUNOL, V145, P161