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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.


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Submitted October 21, 2004
Accepted July 17, 2005

Endogenous NGF regulates CGRP expression in human monocytes and affects HLA-DR, B7 expression and IL-10 production

Luisa Bracci-Laudiero*, Luigi Aloe, Maria C Caroleo, Pasquale Buanne, Nicola Costa, Giuseppe Starace, and Thomas Lundeberg

Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy
Department of Pharmacobiology, University of Calabria, Cosenza, Italy
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy
Faculty of Pharmacy, University of Magna Grecia, Catanzaro, Italy
Rehabilitation Medicine, Karolinska Hospital, Stockholm, Sweden

* 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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