S. Kamphuis et al., ROLE OF ENDOGENOUS PROENKEPHALIN A-DERIVED PEPTIDES IN HUMAN T-CELL PROLIFERATION AND MONOCYTE IL-6 PRODUCTION, Journal of neuroimmunology, 84(1), 1998, pp. 53-60
In this paper, we describe that met-enkephalin and/or enkephalin-conta
ining intermediary peptides of the prohormone pro-enkephalin A are pro
duced and secreted by human peripheral blood T cells and monocytes. Th
e peptides are produced after stimulation with the mitogenic monoclona
l antibodies anti-CD2.1/2.2 and anti-CD28. In monocytes, enkephalin sy
nthesis was induced by stimulation with lipopolysaccharide. We demonst
rate here that these immune cell-derived enkephalins play an important
regulatory role in the immune response. By using an anti-sense oligon
ucleotide strategy we could block the production of enkephalins. Block
ade of the production of met-enkephalin and enkephalin-containing inte
rmediary peptides resulted in enhancement of the proliferative T cell
response and inhibition of monocyte IL-6 secretion. In vitro reconstit
ution of the anti-sense treated cultures with synthetic met-enkephalin
or the delta-type specific opioid receptor agonist deltorphin could r
everse inhibition of monocyte IL-6 production, suggesting that endogen
ous enkephalins act via membrane opioid receptors. In contrast, additi
on of met-enkephalin or deltorphin to the anti-sense treated T cell cu
ltures did not have any effect on T cell proliferation. (C) 1998 Elsev
ier Science B.V.