Mechanisms of oxyradical production in substance P stimulated rheumatoid synovial cells

Tanabe, Takatoshi; Otani, Hitomi; Mishima, Katsuyuki; Ogawa, Ryokei; Inagaki, Chiyoko

doi:10.1007/bf01419729

Cited by 28 publications

(23 citation statements)

References 23 publications

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“…Several studies have reported that SP facilitates lymphocyte proliferation in response to mitogenic stimulation (1,19) and increases cytokine production (6, 7, 20, 22, 36-38, 40, 44, 50). SP has also been shown to regulate macrophage function such as superoxide anion production (8,14,39,57). Macrophages themselves express preprotachykinin mRNA (27,34), suggesting that they may produce SP.…”

Section: Discussionmentioning

confidence: 99%

Respiratory Syncytial Virus Infection and G and/or SH Protein Expression Contribute to Substance P, Which Mediates Inflammation and Enhanced Pulmonary Disease in BALB/c Mice

Tripp

Moore

Winter

et al. 2000

J Virol

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A distinct clinical presentation of respiratory syncytial virus (RSV) infection of humans is bronchiolitis, which has clinical features similar to those of asthma. Substance P (SP), a tachykinin neuropeptide, has been associated with neurogenic inflammation and asthma; therefore, we chose to examine SP-induced inflammation with RSV infection. In this study, we examined the production of pulmonary SP associated with RSV infection of BALB/c mice and the effect of anti-SP F(ab) 2 antibodies on the pulmonary inflammatory response. The peak production of pulmonary SP occurred between days 3 and 5 following primary RSV infection and day 1 after secondary infection. Treatment of RSV-infected mice with anti-SP F(ab) 2 antibodies suggested that SP may alter the natural killer cell response to primary and secondary infection. In mice challenged after formalin-inactivated RSV vaccination, SP appears to markedly enhance pulmonary eosinophilia as well as increase polymorphonuclear cell trafficking to the lung. Based on studies with a strain of RSV that lacks the G and SH genes, the SP response to RSV infection appears to be associated with G and/or SH protein expression. These data suggest that SP may be an important contributor to the inflammatory response to RSV infection and that anti-SP F(ab) 2 antibodies might be used to ameliorate RSV-associated disease.Respiratory syncytial virus (RSV) is one of most important respiratory pathogens of infants and young children worldwide (12,24,28,29,35). Acute bronchiolitis is the most distinctive feature of RSV infection in infants and young children, and RSV is the most important cause of bronchiolitis (26,51,66). Bronchiolitis is an acute inflammatory process of the respiratory bronchioles leading to symptoms of obstructive airway disease. The clinical presentation of bronchiolitis is similar to that of asthma (48,51,64). These similarities have led investigators to consider that the mechanisms underlying RSV bronchiolitis and asthma may be similar (46,48,56,65).Recent studies have raised the possibility that neurogenic factors, including tachykinins such as substance P (SP), may contribute to pulmonary inflammation associated with asthma (4,17,31,59). For example, SP is active at nanomolar concentrations and has diverse actions including induction of vascular extravasation of immune cells (15, 21), increased adhesion of polymorphonuclear cells and eosinophils to endothelium (36), and potentiation of immune functions of lymphocytes, macrophages, mast cells, and eosinophils (42). SP is thought to act primarily through the specific neurokinin 1 receptor (NK-1R) (3,9,10,43). It is possible that SP can also act in a receptorindependent fashion, because it is a small (11-amino-acid) amphiphilic/amphipathic molecule that can pass through the cellular membrane. The functional relevance of SP in pulmonary inflammation is indicated by studies of NK-1R knockout mice (11). In these studies, immune complexes, which induce vascular permeability and allow infiltration of inflammatory cells into...

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Section: Discussionmentioning

confidence: 99%

Respiratory Syncytial Virus Infection and G and/or SH Protein Expression Contribute to Substance P, Which Mediates Inflammation and Enhanced Pulmonary Disease in BALB/c Mice

Tripp

Moore

Winter

et al. 2000

J Virol

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“…Synovial cells were isolated as described by Tanabe et al (4). Surface parts of synovial tissues dissected from the knee joints of conventional Japanese white rabbits (2.8 to 3.0 kg body wt.)…”

Section: Preparation Of Synovial Cellsmentioning

confidence: 99%

Molecular Mechanisms for α2-Adrenoceptor-Mediated Regulation of Synoviocyte Populations

Mishima

Otani

Tanabe

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-The sympathetic nervous system has been indicated to influence the severity of inflammatory disease including rheumatoid arthritis. In this study, we elucidated the effects of catecholamine on the synovial cell populations. Stimulation with epinephrine or norepinephrine for 1 -2 weeks dose-and time-dependently increased the number of synovial A (macrophage-like) cells but decreased that of B (fibroblast-like) cells. These responses in A and B cells were inhibited by the a 2-antagonist yohimbine, the G-protein inactivator pertussis toxin and the phospholipase C (PLC) inhibitor U-73122. Furthermore, the protein kinase C (PKC) inhibitor calphostin C and mitogen-activated protein (MAP) kinase inhibitors PD98059 and wortmannin also abolished the norepinephrine effects on A and B cell numbers. In A cells cloned from an A and B cell mixture, norepinephrine also increased the cell number. In immunoblotting and immunocytostaining analyses, among the PKC isozymes, only PKC b II immunoreactivity was observed in the cytoplasm of unstimulated A and B cells. After a 2-adrenoceptor stimulation, PKC b II immunoreactivity increased in the plasma membranes of both A and B cells with decreases in the cytoplasm. These findings indicated that a 2-adrenoceptor stimulation of type A and B synoviocytes produced an increase and a decrease in the respective cell number, probably through Gi-coupled PLC activation and the resulting stimulation of the PKC bII /MAP kinase.

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“…PKC activation and [Ca2+] i mobilization were measured as described in Materials and methods. n = 15) by 70-90 s after the stimulation and again increased gradually to a plateau level (138.5 + 9.0 nM, n = 15) by 5 rain; this level was maintained for at least 10 min [8]. In the subsequent experiments, the responses were represented as A[Ca2+]i increases.…”

Section: Resultsmentioning

confidence: 98%

“…For example, substance P, which is released from the sensory C-fiber endings in response to noxious stimuli, induces the release of histamine and prostaglandin E2 from synoviocytes and leukocytes, and is thus a potent mediator of inflammation [6,9,10]. The stimulation of synviocytes and other cells with substance P has been reported to induce superoxide anion and interleukin (IL)-lfl production associated with the accumulation of inositol phosphates, and this results in protein kinase C (PKC) activation [8,[11][12][13]. Thus, although the intracellular signalling mechanisms which trigger the cytokine production of several types of cells are being clarified, the intracellular events which underlie the cells' priming mechanisms remain unclear [2][3][4][5].…”

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confidence: 99%

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Substance P-induced priming effects on synovial cells

Komuro

Tanabe

Ogushi

et al. 1999

Japanese Journal of Rheumatology

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Abstract--We detected and analyzed an intracellular mechanism of a substance P-induced priming effect on cytokine production using human synovial cells. The synovial tissues were isolated from the knee joints of osteoarthritis patients. After the administration of a low dose of substance P (1 nM) without significant effect alone, the synovial cells were stimulated with substance P (30/zM), phorbol 12-myristate 13-acetate (PMA) (100 nM), and calcium ionophore (A23187) (1/zM). The total interleukin (IL)-l/3 and IL-6 levels in the supernatant was measured by an enzymelinked immunosorbent assay (ELISA) kit, and the changes in the intracellular calcium concentration ([Ca2+]i) and protein kinase C (PKC) activation were measured by the fura 2-AM fluorescence method and a radioimmunoassay, respectively. The substance P-induced cytokine production was accompanied by an elevation of [Ca 2+ ]i and PKC activation. The amounts of cytokines produced from the substance P (1 nM)-primed synovial cells stimulated with 30 #M substance P were approximately 4 times as much as that observed in non-primed cells. In addition, the priming treatment with 1 nM substance P enhanced not only the subsequent substance P-induced cytokine production, but also the PMA-induced response. However, substance P (1 nM) priming treatment did not affect the A23187-induced response. Furthermore, in substance P-primed cells, substance P (30/zM) induced a significant activation of PKC without changing the [Ca2+]i elevation response. These results suggest that the substance P-priming effect on synovial cells contributed to changes in intracellular mechanisms such as PKC activation.

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Mechanisms of oxyradical production in substance P stimulated rheumatoid synovial cells

Cited by 28 publications

References 23 publications

Respiratory Syncytial Virus Infection and G and/or SH Protein Expression Contribute to Substance P, Which Mediates Inflammation and Enhanced Pulmonary Disease in BALB/c Mice

Respiratory Syncytial Virus Infection and G and/or SH Protein Expression Contribute to Substance P, Which Mediates Inflammation and Enhanced Pulmonary Disease in BALB/c Mice

Molecular Mechanisms for α2-Adrenoceptor-Mediated Regulation of Synoviocyte Populations

Substance P-induced priming effects on synovial cells

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