Effects of tenidap on Ca2+- and protein kinase C-mediated protein phosphorylation, activation of the arachidonate-mobilizing phospholipase A2 and subsequent eicosanoid formation in macrophages

Bondeson, Jan; Sundler, Roger

doi:10.1016/0006-2952(94)90154-6

Cited by 10 publications

(5 citation statements)

References 20 publications

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“…Our findings support this hypothesis. This activated pathway could modulate intracellular signaling systems and further induce the production of inflammatory mediators, 20,21 and finally might affect other metabolic pathways.…”

Section: Discussionmentioning

confidence: 99%

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Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry

Lü

Zha

et al. 2012

Mol. BioSyst.

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Rheumatoid arthritis (RA) is the most severe type of chronic inflammatory disease and has always been a research hotspot in different fields. In this study, a non-targeted metabonomics approach was carried out to profile metabolic characteristics of RA and its Chinese medicine subtypes by using liquid chromatography-mass spectrometry (LC-MS) and gas chromatographymass spectrometry (GC-MS). Plasma samples of 57 RA patients and 23 healthy controls were collected. On the basis of the traditional Chinese medicine (TCM), RA patients were classified into two main patterns, the cold pattern and the heat pattern. By using univariate and multivariate data analysis, we found that the RA patients presented diverse dysfunctions in inositol phosphate metabolism, lipid metabolism, amino acid metabolism, glucose metabolism, ascorbate metabolism, glyoxylate and dicarboxylate metabolism. The metabolic phenotypes were different between the RA cold pattern and the RA heat pattern. Compared with the RA cold pattern, the RA heat pattern showed elevated plasma concentrations of glycochenodeoxycholate, proline, saturated and mono-unsaturated phosphatidylcholine (PC) but decreased levels of urea, free fatty acid (FFA) and polyunsaturated PC. Our data show that metabonomics is a valuable tool in disease and TCM subtype research.

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Section: Discussionmentioning

confidence: 99%

“…For each dried sample, 65 mL of methoxyamine hydrochloride (20 , where it was held for 5 min. Helium was used as the carrier gas with a constant velocity of 1.0 mL min À1 and the split ratio was 10 : 1.…”

Section: Gc-ms Analysismentioning

confidence: 99%

Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry

Lü

Zha

et al. 2012

Mol. BioSyst.

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“…Since tenidap is a potent anion-transport inhibitor and modulator of intracellular pH, it is possible that tenidap's effects on chemokine production, similar to what occurs with IL-6 and IL-1b production, could be attributed to changes in intracellular pH and anion transport. Tenidap also modifies the activation-induced calcium fluxes in several cells, such as mast cells and T cells [41] and the intracellular protein phosphorylation activity in activated macrophages [42].…”

Section: Discussionmentioning

confidence: 99%

Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression in the synovial tissue of rabbits with antigen arthritis and in cultured synovial cells

Palacios

López-Armada

Hernández

et al. 1998

Clinical and Experimental Immunology

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Since IL-8 and MCP-1 are chemoattractant proteins that participate in the recruitment of inflammatory cells into the arthritic joint, we examined the effects of tenidap, a new anti-inflammatory drug of the oxindole family, on IL-8 and MCP-1 expression in the joints of rabbits with acute antigen arthritis. The model was induced by injecting 5 mg/ml ovalbumin into the knees of 20 preimmunized rabbits. Animals were randomized into two groups: treated with tenidap (15 mg/kg per 12 h), or untreated. The effect of tenidap treatment was evaluated on chemokine production in synovial membranes of rabbits with arthritis and in cultured monocytic and synovial cells (SC). By immunoperoxidase staining, chemokines were localized in the synovial tissue. Chemokine messenger RNA levels in the synovial membranes and in cultured cells were analysed by reverse transcription-polymerase chain reaction (RT-PCR). At the end of the study, tenidap significantly reduced neutrophil infiltration into the joint cavity (27+/-4 x 10(6) cells/ml versus 45+/-6 x 10(6) cells/ml in untreated; P<0.05), and synovial effusion (134+/-15 microl versus 236+/-19 microl in untreated; P<0.005). Untreated rabbits showed synovial membrane up-regulation in mRNA expression of IL-8 and MCP-1 (11- and seven-fold versus healthy rabbits, respectively) that was markedly decreased by tenidap (two- and three-fold versus healthy rabbits, respectively). IL-8 and MCP-1 were localized in the synovial tissue in a perivascular pattern and areas of the interstitium and lining, mostly coinciding with cell infiltration. Tenidap also reduced the accumulation of IL-8 and MCP-1 proteins. In cultured synovial and monocytic cells, tumour necrosis factor-alpha (TNF-alpha) elicited an increase in gene expression of IL-8 (four- and nine-fold, respectively) and MCP-1 (nine- and four-fold, respectively) that was significantly reversed in both cell types by 10 microM tenidap. These results suggest that the beneficial effect of tenidap in acute antigen arthritis could be related to the down-regulation in gene expression and synthesis of IL-8 and MCP-1, two key chemokines involved in the recruitment of inflammatory cells.

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“…This implies that the inhibition curves for tenidap's two effects on 5-LO overlap to some extent. Two published reports [53,54] state that tenidap's in vitro inhibition of the 5-LO pathway results from an action on AA mobilization. One report by Smith et al [53] bases this conclusion on the similar concentration range (10-100 M) for tenidap's inhibition of calcium ionophore induced arachidonic acid deacylation and LTB 4 synthesis by human neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…Bondeson and Sundler [54], using murine peritoneal macrophages, have shown that tenidap interferes with PMA's induction of cytosolic phospholipase A 2 (PLA 2 ) while exerting little effect on basal enzyme activity. From these observations the authors conclude that tenidap does not inhibit PLA 2 directly but that the drug modulates some early step in the signal transduction pathway which can effect the amount of AA available for metabolism.…”

Section: Discussionmentioning

confidence: 99%

Tenidap inhibits 5-lipoxygenase product formation in vitro, but this activity is not observed in three animal models

Carty

Sweeney

Griffiths

et al. 1997

Inflammation Research

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Effects of tenidap on Ca2+- and protein kinase C-mediated protein phosphorylation, activation of the arachidonate-mobilizing phospholipase A2 and subsequent eicosanoid formation in macrophages

Cited by 10 publications

References 20 publications

Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry

Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry

Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression in the synovial tissue of rabbits with antigen arthritis and in cultured synovial cells

Tenidap inhibits 5-lipoxygenase product formation in vitro, but this activity is not observed in three animal models

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