Administration of Nerve Growth Factor (NGF) in EAE models delays the onset and prevents the full development of EAE lesions. In line with the newly found anti-inflammatory activity of NGF are our recent results on the autocrine NGF synthesis in B lymphocytes, which directly regulate in these cells the expression of calciotonin gene-related peptide (CGRP), a neuropeptide which is a potent inhibitor of T cell proliferation and antigen presentation by macrophages and monocytes. Using cultures of human monocytes we investigated by RT-PCR, immunofluorescence and flow cytometry analysis whether NGF can regulate the expression of CGRP also in these cells and influence the expression of B7.1 and B7.2 and IL-10. Our data indicate that monocytes synthesise basal levels of NGF but, after LPS stimulation, up-regulate NGF expression in dose-dependent fashion. When the cultures are deprived of endogenous NGF, CGRP expression in resting cells decreases and the up-regulation of CGRP induced by LPS is prevented. In addition we observed that endogenous NGF reduction affects co-stimulatory molecule expression and IL-10 synthesis, and these effects can be partially mimicked by using CGRP receptor I antagonist. Our findings indicate that endogenous synthesis of NGF in monocytes has a functional role and, by influencing B7.2 expression and IL-10 production, contributes to the down-regulation of the immune response and strongly support the newly found anti-inflammatory activity of NGF.
NGF regulates CGRP expression in human monocytes: effects on B7 expression and IL-10 production.
BracciLaudiero L;
2004
Abstract
Administration of Nerve Growth Factor (NGF) in EAE models delays the onset and prevents the full development of EAE lesions. In line with the newly found anti-inflammatory activity of NGF are our recent results on the autocrine NGF synthesis in B lymphocytes, which directly regulate in these cells the expression of calciotonin gene-related peptide (CGRP), a neuropeptide which is a potent inhibitor of T cell proliferation and antigen presentation by macrophages and monocytes. Using cultures of human monocytes we investigated by RT-PCR, immunofluorescence and flow cytometry analysis whether NGF can regulate the expression of CGRP also in these cells and influence the expression of B7.1 and B7.2 and IL-10. Our data indicate that monocytes synthesise basal levels of NGF but, after LPS stimulation, up-regulate NGF expression in dose-dependent fashion. When the cultures are deprived of endogenous NGF, CGRP expression in resting cells decreases and the up-regulation of CGRP induced by LPS is prevented. In addition we observed that endogenous NGF reduction affects co-stimulatory molecule expression and IL-10 synthesis, and these effects can be partially mimicked by using CGRP receptor I antagonist. Our findings indicate that endogenous synthesis of NGF in monocytes has a functional role and, by influencing B7.2 expression and IL-10 production, contributes to the down-regulation of the immune response and strongly support the newly found anti-inflammatory activity of NGF.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
