Pro- and Anti-Inflammatory Effects of Neuropeptide Y: Induction of Dendritic Cells Migration and Th2 Polarization

Effects Neuropeptide Y Dendritic Cells

A new study in The FASEB Journal indicates that Neuropeptide Y (NPY) is able to promote migration of human monocyte-derived immature dendritic cells (DCs), and a T helper (Th)2 polarization.

NPY is a neurotransmitter released by the sympathetic nervous system along with norepinephrine (noradrenaline), and elevated NPY levels are detected in conditions of acute or chronic psychological stress as well as cold stress.

In recent years, elevated NPY levels have also been implicated in various inflammatory conditions such as asthma, atherosclerosis, rheumatoid arthritis, obesity and cancer, and several studies have suggested NPY as a major factor in the known link between stress and exacerbations of these diseases.

Neuropeptide Y has been shown to inhibit macrophage cytokine production and natural killer (NK) cell activity, while also stimulating the migration of monocytes, endothelial, polymorphonuclear and NK cells, and inducing a Th2 shift.

In the April 03, 2014 online issue of The FASEB Journal, Brigitta Buttari and colleagues from Istituto Superiore di Sanità, and the Institute of Neurobiology and Molecular Medicine, Italian National Research Council, Rome, Italy further characterize some pathways through which NPY impacts the immune system. More specifically, the authors examine the effect of NPY on DCs and their interactions with T cells.

The study finds that NPY is a potent inducer of chemotaxis, adhesion to endothelial cells, and transendothelial migration of human monocyte-derived immature DCs; and identifies that the binding to NPY-Y1R and subsequent ERK and p38 MAPK activation is a possible pathway mediating the chemotactic response.

Furthermore, the study also provides evidence that the NPY-stimulated DCs increase their interleukin (IL)-10 and IL-6 production, thus promoting differentiation of naïve T cells into a Th2 phenotype.

Thus, during an immune/inflammatory response NPY may exert pro-inflammatory effects through the recruitment of immature DCs, but it may exert anti-inflammatory effects by promoting a Th2 polarization.

These findings may also have clinical implications for the well-known stress-induced exacerbations of allergy/asthma and certain autoimmune and rheumatic diseases; or cold weather stress-aggravated rheumatic conditions and/or cardiovascular incidents.

Understanding the role and specific actions of NPY in inflammatory diseases can have major clinical implications and may stimulate future research to investigate the potential of NPY as a diagnostic or prognostic marker or therapeutic target.

Source: FASEB J, 2014, Apr 3. [Epub ahead of print], doi: 10.1096/fj.13-243485
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Cover Image Credit: Bone marrow-derived dendritic cell (BMDC) morphology by scanning electron microscopy (SEM). (A) SEM image (500Â magnification) of immature dendritic cells (DCs) formed by monocytes after 6 days of induction; (B) SEM image (500Â magnification) of mature DCs formed by monocytes after 8 days of induction; (C) SEM image (4KÂ magnification) of immature DCs formed by monocytes after 6 days of induction; (D) SEM image (4KÂ magnification) of mature DCs formed by monocytes after 8 days of induction. From: Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products; Open Access: