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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.
IMMUNOBIOLOGY Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 productionFrom the Institute of Neurobiology and Molecular Medicine CNR, Rome, Italy; the Department of Pharmacobiology, University of Calabria, Cosenza, Italy; the Deparment of Experimental Medicine, University of L'Aquila, L'Aquila, Italy; the Faculty of Pharmacy, University of Magna Grecia, Catanzaro, Italy; and Rehabilitation Medicine, Karolinska Hospital, Stockholm, Sweden.
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 neutralized, the up-regulation of CGRP expression induced by LPS is inhibited. The expression of membrane molecules involved in T-cell activation such as human leukocyte antigen-DR (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 interleukin 10 (IL-10) synthesis. Our findings indicate that endogenous NGF synthesis has a functional role and may represent a physiologic mechanism to down-regulate major histocompatibility complex (MHC) class II and CD86 expression and alter the development of immune responses.
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