Role of endogenous pro-enkephalin A-derived peptides in human T cell proliferation and monocyte IL-6 production

被引:49
作者
Kamphuis, S [1 ]
Eriksson, F [1 ]
Kavelaars, A [1 ]
Zijlstra, J [1 ]
van de Pol, M [1 ]
Kuis, W [1 ]
Heijnen, CJ [1 ]
机构
[1] Univ Hosp Children & Youth Het Wilhelmina Kinderz, Dept Immunol, NL-3501 CA Utrecht, Netherlands
关键词
enkephalins; anti-sense oligonucleotide; T cells; monocytes; neuroimmunomodulation; opioids;
D O I
10.1016/S0165-5728(97)00240-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this paper, we describe that met-enkephalin and/or enkephalin-containing intermediary peptides of the prohormone pro-enkephalin A are produced and secreted by human peripheral blood T cells and monocytes. The peptides are produced after stimulation with the mitogenic monoclonal antibodies anti-CD2.1/2.2 and anti-CD28. In monocytes, enkephalin synthesis was induced by stimulation with lipopolysaccharide. We demonstrate here that these immune cell-derived enkephalins play an important regulatory role in the immune response. By using an anti-sense oligonucleotide strategy we could block the production of enkephalins. Blockade of the production of met-enkephalin and enkephalin-containing intermediary peptides resulted in enhancement of the proliferative T cell response and inhibition of monocyte IL-6 secretion. In vitro reconstitution of the anti-sense treated cultures with synthetic met-enkephalin or the delta-type specific opioid receptor agonist deltorphin could reverse inhibition of monocyte IL-6 production, suggesting that endogenous enkephalins act via membrane opioid receptors. In contrast, addition of met-enkephalin or deltorphin to the anti-sense treated T cell cultures did not have any effect on T cell proliferation. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:53 / 60
页数:8
相关论文
共 48 条
[1]   REGULATION OF PROENKEPHALIN A MESSENGER-RIBONUCLEIC-ACID LEVELS IN NORMAL LYMPHOCYTE-B - SPECIFIC-INHIBITION BY GLUCOCORTICOID HORMONES AND SUPERINDUCTION BY CYCLOHEXIMIDE [J].
BEHAR, OZ ;
OVADIA, H ;
POLAKIEWICZ, RD ;
ABRAMSKY, O ;
ROSEN, H .
ENDOCRINOLOGY, 1991, 129 (02) :649-655
[2]   Immune-neuro-endocrine interactions: Facts and hypotheses [J].
Besedovsky, HO ;
DelRey, A .
ENDOCRINE REVIEWS, 1996, 17 (01) :64-102
[3]  
BIRCH NP, 1987, J BIOL CHEM, V262, P3382
[4]   THE SYNTAX OF IMMUNE-NEUROENDOCRINE COMMUNICATION [J].
BLALOCK, JE .
IMMUNOLOGY TODAY, 1994, 15 (11) :504-511
[5]   BREAKDOWN OF SMALL ENKEPHALIN DERIVATIVES AND ADRENAL PEPTIDE-E BY HUMAN-PLASMA [J].
BOARDER, MR ;
MCARDLE, W .
BIOCHEMICAL PHARMACOLOGY, 1986, 35 (06) :1043-1047
[6]   INTERLEUKIN-1 IMMUNOREACTIVE INNERVATION OF THE HUMAN HYPOTHALAMUS [J].
BREDER, CD ;
DINARELLO, CA ;
SAPER, CB .
SCIENCE, 1988, 240 (4850) :321-324
[7]   EVIDENCE FOR A DELTA-CLASS OPIOID RECEPTOR ON CELLS OF THE IMMUNE-SYSTEM [J].
CARR, DJJ ;
KIM, CH ;
DECOSTA, B ;
JACOBSON, AE ;
RICE, KC ;
BLALOCK, JE .
CELLULAR IMMUNOLOGY, 1988, 116 (01) :44-51
[9]   NEUROIMMUNOMODULATION WITH ENKEPHALINS - ENHANCEMENT OF HUMAN NATURAL-KILLER (NK) CELL-ACTIVITY INVITRO [J].
FAITH, RE ;
LIANG, HJ ;
MURGO, AJ ;
PLOTNIKOFF, NP .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1984, 31 (03) :412-418
[10]   THE IMMUNE LOGICAL BRAIN [J].
FARRAR, WL ;
HILL, JM ;
HARELBELLAN, A ;
VINOCOUR, M .
IMMUNOLOGICAL REVIEWS, 1987, 100 :361-378