FK506 suppresses the stimulation of matrix metalloproteinase 13 synthesis by interleukin-1β in rheumatoid synovial fibroblasts

Migita, Kiyoshi; Miyashita, Taichiro; Maeda, Yümi; Aoyagi, Takahiko; Kawabe, Yojiro; Nakamura, Minoru; Yatsuhashi, Hiroshi; Ishibashi, Hiromi; Eguchi, Katsumi

doi:10.1016/j.imlet.2004.11.014

Cited by 16 publications

(12 citation statements)

References 22 publications

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“…Although an inflammatory reaction and oxidative stress have been found to be strongly associated with myocardial damage, the exact signaling pathways involved in the perpetuation of myocardial damage, LV dysfunction, and cardiac remodeling remain unclear. Previous studies have shown that the MAPK pathway is frequently up-regulated by environmental and oxidative stresses as well as inflammatory and cytokine stimulations, thereby leading to cell apoptosis and inflammatory cytokine production [12][13][14][15][16][17] . On the other hand, the Akt signaling pathway has been shown to be an essential contributor to vascular smooth muscle cell migration and proliferation in response to mechanical stress 18) .…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the Akt signaling pathway has been shown to be an essential contributor to vascular smooth muscle cell migration and proliferation in response to mechanical stress 18) . Interestingly, tacrolimus has been proved to effectively inhibit both MAPK and Akt signal pathways 17,[21][22][23] . The results of the present study showed not only the notable augmentation of inflammation, oxidative stress, and α-SMA expression, which reflected cardiofibroblast proliferation, but also marked enhancement of the expression of MAPK (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the MAPK pathway is activated in response to environmental and oxidative stresses, cellular proliferation and apoptosis, as well as inflammation and cytokine stimulation [12][13][14][15][16][17] . Another kinase signaling pathway, the PI-3 kinase/Akt signal pathway, has been shown to participate in the modulation of vascular smooth muscle cell migration and proliferation in response to mechanical stress 18) ; however, whether MAPK and PI-3 kinase/Akt signaling pathways are associated with the inflammatory response, generation of oxidative stress, increased infarct size and cardiac remodeling after AMI is currently unclear.…”

Section: Animal Model Of Ami and Rationale Of Tacrolimus Dosage For Ementioning

confidence: 99%

“…FK506 forms the FK506-binding protein (FK-BP) in cytoplasmic receptor that inactivates calcineurin, a central phosphatase for T cell signaling 20) . Experimental studies have revealed that tacrolimus treatment effectively inhibits both MAPK and PI-3 kinase/Akt signaling pathways in various disease settings 17,[21][22][23] . Thus, we propose that inhibition of MAPK and PI-3 kinase/Akt signaling pathways by tacrolimus may attenuate inflammation, oxidative stress, and cardiac remodeling as well as improving heart function after AMI.…”

Section: Animal Model Of Ami and Rationale Of Tacrolimus Dosage For Ementioning

confidence: 99%

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Effect of Tacrolimus on Myocardial Infarction Is Associated with Inflammation, ROS, MAP Kinase and Akt Pathways in Mini-Pigs

Yang¹,

Sheu²,

Tsai³

et al. 2013

JAT

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Aim: This study tested the hypothesis that tacrolimus therapy limited left ventricular (LV) infarct and remodeling by suppressing the inflammatory response, oxidative stress and regulating the mitogen-activated protein kinase (MAPK) and Akt signaling pathways in an acute myocardial infarction (AMI) mini-pig model by ligating the left anterior descending coronary artery (LAD). Methods: Twelve male mini-pigs were equally randomized into AMI treated by saline (3.0 mL) (AMIS), and AMI treated by tacrolimus (0.5 mg) (AMIT). Thirty minutes after the procedure, intra-LAD injections were performed just beyond the ligation. Results: Inflammatory biomarkers at transcription or protein levels [matrix metalloproteinase (MMP-9), plasminogen activator inhitor-1, tumor necrotic factor (TNF-α), nuclear factor (NF)-κB] and the cellular level (CD40＋ cells) were markedly higher in AMIS than in AMIT animals (all p＜0.001). Fibrosis biomarkers at the protein level (α-smooth muscle actin, transforming growth factor-β) and Sirius-red staining were notably higher in AMIS than in AMIT animals (all p＜0.03). Antioxidant biomarkers at protein or transcription levels (heme oxygenase-1, quinone oxidoreductase-1, glutathione reductase, glutathione peroxidase) were significantly higher in AMIS than in AMIT animals (all p＜0.01). Protein expressions of ERK1, p38 MAPK and Akt were markedly increased in AMIS compared to AMIT animals (all p＜0.001). Significantly aggravated LV infarction and remodeling were noted in AMIS compared to AMIT animals, whereas LV ejection fraction was markedly decreased in AMIS compared to AMIT animals (all p＜0.001). Conclusions: Intra-coronary administration of tacrolimus attenuated inflammation and MAPK signaling, limited infarct size, and preserved LV function. J Atheroscler Thromb, 2013; 20:9-22.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Animal Model Of Ami and Rationale Of Tacrolimus Dosage For Ementioning

confidence: 99%

Section: Animal Model Of Ami and Rationale Of Tacrolimus Dosage For Ementioning

confidence: 99%

See 2 more Smart Citations

Effect of Tacrolimus on Myocardial Infarction Is Associated with Inflammation, ROS, MAP Kinase and Akt Pathways in Mini-Pigs

Yang¹,

Sheu²,

Tsai³

et al. 2013

JAT

View full text Add to dashboard Cite

show abstract

“…The 5Ј flanking region of the MCP-1 gene contains multiple binding sites for AP-1 (47) and activation of AP-1 is required for induction of MCP-1 by cytokines, growth factors, LPS, and mechanical stress in various cells (19, 48 -50). AP-1 is activated by IL-1, which may be inhibited by CsA or FK506 in some cell types (51,52). AP-1 is a possible candidate responsible for the NF-B-independent induction of MCP-1 in IL-1␤-stimulated tubular cells.…”

Section: Discussionmentioning

confidence: 99%

Suppression of NF-κB by Cyclosporin A and Tacrolimus (FK506) via Induction of the C/EBP Family: Implication for Unfolded Protein Response

Hiramatsu

Hayakawa

et al. 2009

The Journal of Immunology

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Immunosuppressive agents cyclosporin A (CsA) and tacrolimus (FK506) inhibit cytokine production by activated lymphocytes through interfering with calcineurin. However, little is known about their effects on the function of nonlymphoid cells. We found that, in renal tubular cells, induction of MCP-1 by inflammatory cytokines was blunted by CsA and FK506. This suppression was correlated with induction of unfolded protein response (UPR) evidenced by endogenous and exogenous indicators. The induction of UPR by these agents was reversible and observed generally in other nonimmune cells. Furthermore, administration with CsA in reporter mice caused rapid, systemic induction of UPR in vivo. In TNF-α-treated cells, suppression of MCP-1 by CsA or FK506 was associated with blunted responses of NF-κB, the crucial regulator of MCP-1. The suppression of NF-κB was reproduced by other inducers of UPR including AB5 subtilase cytotoxin, tunicamycin, thapsigargin, and A23187. CsA and FK506, as well as other UPR inducers, caused up-regulation of C/EBP family members, especially C/EBPβ and CHOP (C/EBP homologous protein), and overexpression of either C/EBPβ or CHOP significantly attenuated TNF-α-triggered NF-κB activation. Furthermore, down-regulation of C/EBPβ by small interfering RNA substantially reversed the suppressive effect of CsA on TNF-α-induced MCP-1 expression. These results suggested that CsA and FK506 confer insensitiveness to TNF-α on resident cells through UPR-dependent induction of the C/EBP family members.

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FK506 inhibition of gliostatin/thymidine phosphorylase production induced by tumor necrosis factor-α in rheumatoid fibroblast-like synoviocytes

et al. 2010

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Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities. The purpose of this study was to determine the inhibitory effects of FK506 (tacrolimus) on GLS production in rheumatoid arthritis (RA). We investigated the modulation of serum GLS by FK506 therapy and the effect of FK506 on the production of GLS in fibroblast-like synoviocytes (FLSs). Serum samples were collected from 11 RA patients with active disease at baseline and after 12 weeks of FK506 treatment. Serum concentrations of GLS and matrix metalloproteinase (MMP)-3 were measured by ELISA and found to be down-regulated in responders evaluated with a disease activity score. Patient FLSs were cultured and stimulated by tumor necrosis factor (TNF)-α with or without FK506. The expression levels of GLS were determined using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme immunoassay and shown to be significantly increased. GLS levels in TNF-α-stimulated FLSs were reduced by FK506 treatment. Our data show a novel mechanism for the action of physiological concentrations of FK506 in RA that regulates the production of GLS in FLSs.

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FK506 suppresses the stimulation of matrix metalloproteinase 13 synthesis by interleukin-1β in rheumatoid synovial fibroblasts

Cited by 16 publications

References 22 publications

Effect of Tacrolimus on Myocardial Infarction Is Associated with Inflammation, ROS, MAP Kinase and Akt Pathways in Mini-Pigs

Effect of Tacrolimus on Myocardial Infarction Is Associated with Inflammation, ROS, MAP Kinase and Akt Pathways in Mini-Pigs

Suppression of NF-κB by Cyclosporin A and Tacrolimus (FK506) via Induction of the C/EBP Family: Implication for Unfolded Protein Response

FK506 inhibition of gliostatin/thymidine phosphorylase production induced by tumor necrosis factor-α in rheumatoid fibroblast-like synoviocytes

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