INTERLEUKIN-6 (IL-6) GENE-EXPRESSION AND SECRETION BY CYTOKINE-STIMULATED HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS

被引:112
作者
ELNER, VM
SCALES, W
ELNER, SG
DANFORTH, J
KUNKEL, SL
STRIETER, RM
机构
[1] UNIV MICHIGAN,KELLOGG EYE CTR,DEPT OPHTHALMOL,1000 WALL ST,ANN ARBOR,MI 48109
[2] UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109
[3] UNIV MICHIGAN,DEPT SURG,ANN ARBOR,MI 48109
[4] UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109
关键词
RETINAL PIGMENT EPITHELIUM; INTERLEUKIN-6; CYTOKINES; INTERLEUKIN-1; TUMOR NECROSIS FACTOR; LIPOPOLYSACCHARIDE;
D O I
10.1016/0014-4835(92)90048-W
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Retinal and choroidal inflammatory lesions are important causes of visual loss, but the mechanisms regulating intraocular inflammation remain poorly understood. By virtue of its position at the blood-retina barrier, the retinal pigment epithelium (RPE) cells may be critical to the initiation and propagation of ocular inflammation. Previously we showed that cytokine-stimulated RPE cells produce interleukin-8, a well-defined chemotactic factor for neutrophils and lymphocytes. In this study, we found that human RPE cells stimulated by human recombinant interleukin-1-β (rIL-1β) or tumor necrosis factor-α (rTNF-α) produce interleukin-6 (IL-6). Using a plasmacytoma proliferation assay, significant levels of IL-6 were found in media of RPE cells stimulated with either rIL-1β or rTNF-α for 4 hr. Progressive accumulation of IL-6 in media overlying stimulated RPE cells occurred over the subsequent 20 hr. IL-1β was a significantly more potent stimulator of RPE IL-6 production than TNF-α. RPE IL-6 production in response to each of these cytokines was also dose-dependent over a range of 20 pg to 20 ng ml-1. Specific anti IL-6 antibody, but not control immunoglobulin, neutralized RPE-derived IL-6 activity in the plasmacytoma proliferation assays. RPE IL-6 mRNA levels were detectable 1 hr after cytokine stimulation, plateaued within 8 hr in 24-hr assays, and demonstrated dose-dependent kinetics in 6 hr assays. Lipopolysaccharide failed to induce RPE IL-6 mRNA expression or RPE IL-6 production. Our findings indicate that RPE cells express IL-6 mRNA and secrete biologically active IL-6 when stimulated by inflammatory cytokines. RPE IL-6 secretion may be important in ocular lesions involving differentiation and activation of lymphocytes. © 1992.
引用
收藏
页码:361 / 368
页数:8
相关论文
共 53 条
[31]   IL1 INDUCES PROLIFERATION AND IL6 MESSENGER-RNA EXPRESSION IN A HUMAN ASTROCYTOMA CELL-LINE - POSITIVE AND NEGATIVE MODULATION BY CHORELA TOXIN AND CAMP [J].
KASAHARA, T ;
YAGISAWA, H ;
YAMASHITA, K ;
YAMAGUCHI, Y ;
AKIYAMA, Y .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 167 (03) :1242-1248
[32]   CACHECTIN TNF AS WELL AS INTERLEUKIN-1 INDUCES PROSTACYCLIN SYNTHESIS IN CULTURED VASCULAR ENDOTHELIAL-CELLS [J].
KAWAKAMI, M ;
ISHIBASHI, S ;
OGAWA, H ;
MURASE, T ;
TAKAKU, F ;
SHIBATA, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 141 (02) :482-487
[34]   THE BIOLOGY OF INTERLEUKIN-6 [J].
KISHIMOTO, T .
BLOOD, 1989, 74 (01) :1-10
[35]   MOLECULAR REGULATION OF LYMPHOCYTE-B RESPONSE [J].
KISHIMOTO, T ;
HIRANO, T .
ANNUAL REVIEW OF IMMUNOLOGY, 1988, 6 :485-512
[36]   THE NEUTROPHIL-ACTIVATING PROTEIN (NAP-1) IS ALSO CHEMOTACTIC FOR LYMPHOCYTES-T [J].
LARSEN, CG ;
ANDERSON, AO ;
APPELLA, E ;
OPPENHEIM, JJ ;
MATSUSHIMA, K .
SCIENCE, 1989, 243 (4897) :1464-1466
[37]  
LE JM, 1989, LAB INVEST, V61, P588
[38]   IMMUNE-MECHANISMS IN CHOROIDORETINAL INFLAMMATION IN MAN [J].
LIGHTMAN, S ;
CHAN, CC .
EYE, 1990, 4 :345-353
[39]   B-CELL STIMULATING FACTOR-2/INTERLEUKIN-6 IS A COSTIMULANT FOR HUMAN THYMOCYTES AND LYMPHOCYTES-T [J].
LOTZ, M ;
JIRIK, F ;
KABOURIDIS, P ;
TSOUKAS, C ;
HIRANO, T ;
KISHIMOTO, T ;
CARSON, DA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 167 (03) :1253-1258
[40]  
MARMOR MF, 1979, RETINAL PIGMENT EPIT