Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 production.
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 CGRP(1) 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.
Bracci-Laudiero
Luisa
L
Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy. luisa.braccilaudiero@inmm.cnr.it
Aloe
Luigi
L
Caroleo
Maria Cristina
MC
Buanne
Pasquale
P
Costa
Nicola
N
Starace
Giuseppe
G
Lundeberg
Thomas
T
D001402:B-Lymphocytes / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis* / Q000276:immunology; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000276:immunology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D020932:Nerve Growth Factor / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D051940:B7-2 Antigen; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D016753:Interleukin-10; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide