Reduction in serum levels of substance P in patients with rheumatoid arthritis by etanercept, a tumor necrosis factor inhibitor

Origuchi, Tomoki; Iwamoto, Naoki; Kawashiri, Shin‐ya; Fujikawa, Keita; Aramaki, Toshiyuki; Tamai, Mami; Arima, Kei; Nakamura, Hideki; Yamasaki, Satoshi; Ida, Hiroaki; Kawakami, Atsushi; Ueki, Yukitaka; Matsuoka, Naoki; Nakashima, Munetoshi; Mizokami, Akinari; Kawabe, Yojiro; Mine, Masanobu; Fukuda, Takaaki; Eguchi, Katsumi

doi:10.1007/s10165-010-0384-5

Cited by 13 publications

(5 citation statements)

References 33 publications

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“…Independent reports have shown that mast cells, SP, IL-33, and TNF contribute to the inflammatory processes in these diseases (31,(47)(48)(49)(50)(51); for example, increased SP plasma levels (0.31 μg/L) that correlate with mast cell load have been reported in patients with mastocytosis (52). In addition, treatment with the TNF inhibitor etanercept has been shown to reduce serum SP levels in patients with rheumatoid arthritis (53). Our findings provide insight into how SP, IL-33, TNF, and mast cells may interact in these inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors

Taracanova

Alevizos

Karagkouni

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

122

107

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The peptide substance P (SP) and the cytokine tumor necrosis factor (TNF) have been implicated in inflammatory processes. Mast cells are recognized as important in inflammatory responses. Here, we report that IL-33 (30 ng/mL), a member of the IL-1 family of cytokines, administered in combination with SP (1 μM), markedly increase (by 1,000-fold) TNF gene expression in cultured human LAD2 and primary mast cells derived from umbilical cord blood. SP (0.01-1 μM) and IL-33 (1-100 ng/mL) in combination also greatly stimulate TNF secretion (by 4,500-fold). Pretreatment of LAD2 cells with two different neurokinin-1 (NK-1) receptor antagonists and siRNA inhibits TNF secretion by 50% (P < 0.001) when stimulated by SP and IL-33. Pretreatment of LAD2 cells with a neutralizing antibody for IL-33 receptor, ST2, inhibits TNF secretion by 50% (P < 0.001), and ST2 siRNA decreases TNF secretion by 30% (P < 0.05), when stimulated by SP and IL-33. Surprisingly, NK-1 antagonists also inhibit 50% of TNF secretion (P < 0.001) when stimulated only by IL-33, and ST2 receptor reduction also decreases SP-stimulated TNF secretion by 30% (P < 0.05), suggesting an interaction between NK-1 and ST2 receptors. Moreover, IL-33 increases NK-1 gene and surface protein expression, as well as IKβ-α phosphorylation. Pretreatment of LAD2 cells with 5,7,3′,4′-tetramethoxyflavone (methoxyluteolin) (1-100 μM) inhibits (P < 0.001) TNF gene expression (98%) and secretion (64%) at 50 μM and phosphorylation of p-IKB-α at 1 μM when stimulated by SP and IL-33. These findings identify a unique amplification process of TNF synthesis and secretion via the interaction of NK-1 and ST2 receptors inhibitable by methoxyluteolin. mast cells | substance P | interleukin-33 | tumor necrosis factor | inflammation

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Section: Discussionmentioning

confidence: 99%

SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors

Taracanova

Alevizos

Karagkouni

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

122

107

View full text Add to dashboard Cite

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“…Additionally, reduction in CGRP tissue expression levels was seen in the dorsal root ganglia of rats injected with Entanercept (anti-TNFα treatment) (Horii et al, 2010). In both rats and humans with rheumatoid arthritis, CGRP and SP levels were reduced by 50% in the serum after treating with Etanercept (Origuchi et al, 2010). By contrast, TRPV1 activation via capsaicin and SA13353 (capsaicin analog) attenuated LPS-induced TNFα release in serum, and this effect was partially inhibited with CGRP antagonist treatment and in TRPV1 −/− or sensory denervated mice (Tsuji et al, 2009) suggesting a regulatory function for CGRP on TNFα i.e., CGRP is able to downregulate TNFα in vivo .…”

Section: Cgrp and Tnfα: A New Chaptermentioning

confidence: 99%

Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

2014

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The question of how the neural and immune systems interact in host defense is important, integrating a system that senses the whole body with one that protects. Understanding the mechanisms and routes of control could produce novel and powerful ways of promoting and enhancing normal functions as well as preventing or treating abnormal functions. Fragmentation of biological research into specialities has resulted in some failures in recognizing and understanding interactions across different systems and this is most striking across immunology, hematology, and neuroscience. This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems. However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals. But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body. In this review we will therefore focus on the induction of CGRP and its key role in the neuroimmune axis.

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“…36 Notably, in diabetes mellitus and inflammatory disorders, the peripheral nervous system has been identified as a common cause of connective tissue healing malfunction and homeostasis. 13,71,74 …”

Section: Epidemiologymentioning

confidence: 99%

Tendinopathy in Sport

2012

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Context: Tendinopathy is increasing in prevalence and accounts for a substantial part of all sports injuries and occupational disorders. Despite the magnitude of the disorder, high-quality scientific data on etiology and available treatments have been limited. Evidence Acquisition: The authors conducted a MEDLINE search on tendinopathy, or “tendonitis” or “tendinosis” or “epicondylitis” or “jumpers knee” from 1980 to 2011. The emphasis was placed on updates on epidemiology, etiology, and recent patient-oriented Level 1 literature. Results: Repetitive exposure in combination with recently discovered intrinsic factors, such as genetic variants of matrix proteins, and metabolic disorders is a risk factor for the development of tendinopathy. Recent findings demonstrate that tendinosis is characterized by a fibrotic, failed healing response associated with pathological vessel and sensory nerve ingrowth. This aberrant sensory nerve sprouting may partly explain increased pain signaling and partly, by release of neuronal mediators, contribute to the fibrotic alterations observed in tendinopathy. The initial nonoperative treatment should involve eccentric exercise, which should be the cornerstone (basis) of treatment of tendinopathy. Eccentric training combined with extracorporeal shockwave treatment has in some reports shown higher success rates compared to any therapies alone. Injection therapies (cortisone, sclerosing agents, blood products including platelet-rich plasma) may have short-term effects but have no proven long-term treatment effects or meta-analyses to support them. For epicondylitis, cortisone injections have demonstrated poorer long-time results than conservative physiotherapy. Today surgery is less indicated because of successful conservative therapies. New minioperative procedures that, via the endoscope, remove pathologic tissue or abnormal neoinnervation demonstrate promising results but need confirmation by Level 1 studies. Conclusions: Novel targeted therapies are emerging, but multicenter trials are needed to confirm the results of exercise and mini-invasive treatments.

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Reduction in serum levels of substance P in patients with rheumatoid arthritis by etanercept, a tumor necrosis factor inhibitor

Cited by 13 publications

References 33 publications

SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors

SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors

Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

Tendinopathy in Sport

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