Abstract
The neuropeptide substance P (SP) exhibits cytokine-like properties and exerts different effects in autoimmune inflammation. Various immune cells express SP and its neurokinin-1 receptor (NK1R) isoforms. A role for SP has been demonstrated in a number of autoimmune conditions, including multiple sclerosis (MS). In this work, we studied the role of SP and NK1R in human immune cells with a focus on their relationship with IL-12/IL-23 family cytokines and the associated IFN-γ/IL-17. AIMS: (1) To determine the role of SP mediated effects on induction of various inflammatory cytokines in peripheral blood mononuclear cells (PBMC); (2) to investigate the expression of SP and its receptor in T cells and the effects of stimulation with IL-12 and IL-23. Quantitative real-time PCR, flow cytometry, ELISA, promoter studies on PBMC and primary T cells from healthy volunteers, and Jurkat cell line. Treatment with SP significantly increased the expression of IL-12/IL-23 subunit p40, IL-23 p19 and IL-12 p35 mRNA in human PBMC. Expression of NK1R and SP in T cells was upregulated by IL-23 but a trend was observed with IL-12. The IL-23 effect likely involves IL-17 production that additionally mediates IL-23 effects. Mutual interactions exist with SP enhancing the cytokines IL-23 and IL-12, and SP and NK1R expression being differentially but potentially synergistically regulated by these cytokines. These findings suggest a proinflammatory role for SP in autoimmune inflammation. We propose a model whereby immunocyte derived SP stimulates Th1 and Th17 autoreactive cells migrating to the central nervous system (CNS), enhances their crossing the blood brain barrier and perpetuates inflammation in the CNS by being released from damaged nerves and activating both resident glia and infiltrating immune cells. SP may be a therapeutic target in MS.Electronic supplementary materialThe online version of this article (doi:10.1007/s11481-015-9589-x) contains supplementary material, which is available to authorized users.
Highlights
Substance P (SP) is an ubiquitously found 11-amino acid peptide with a number of biological functions
Protein-Level Expression of IL-1β and IL-12p40 in peripheral blood mononuclear cells (PBMC) Stimulated with SP
Because the amounts of IL-12p40 are likely to be too low to correspond to detectable levels of IL-12p70 or IL-23 protein by ELISA, we measured the mRNA expression of the IL-12 family cytokines
Summary
Substance P (SP) is an ubiquitously found 11-amino acid peptide with a number of biological functions. It belongs to the family of tachykinins, which includes neurokinin A, neurokinin B, neuropeptide K, neuropeptide Y, and hemokinin-1. SP is generated through the enzymatic cleavage of pre-pro-tachykinin A, which is encoded by the TAC1 gene. Splice variants of TAC1 generate neurokinin A and neuropeptide K. The role of SP in pain pathways and neurogenic inflammation has been well established, including effects of vasodilatation and plasma extravasation. With its effects on smooth muscle, SP is known to be involved in motility of different organ tracts as well as stimulation of glandular secretion and modulating autonomic reflexes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
