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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3507-3514. Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2004-10-4055.
Submitted October 21, 2004
Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy * Corresponding author; email: luisa.braccilaudiero{at}inmm.cnr.it.
Our recent results on autocrine Nerve Growth Factor (NGF) synthesis in B lymphocytes, which directly regulates the expression and release of calcitonin gene-related peptide (CGRP), a neuropeptide known to down-regulate immune response, led us to propose an anti-inflammatory action of NGF. In the present work we investigated whether the endogenous synthesis of NGF can regulate the expression of CGRP in other antigen-presenting cells, such as monocytes, and whether this may have a functional effect. Our data indicate that human monocytes synthesize basal levels of NGF and CGRP and that, following lipopolysaccharide (LPS) stimulation, NGF and CGRP expression are both up-regulated. When endogenous NGF is neutralised, the up-regulation of CGRP expression induced by LPS is inhibited. The expression of membrane molecules involved in T-cell activation such as HLA-DR and CD86 is affected by endogenous NGF and similar effects were obtained using a CGRP1 receptor antagonist. In addition, NGF deprivation in LPS-treated monocytes significantly decreases IL-10 synthesis. Our findings indicate that endogenous NGF synthesis has a functional role and may represent a physiological mechanism to down-regulate MHC class II and CD86 expression and alter the development of immune responses.
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