Haem oxygenase-1 counteracts the effects of interleukin-1β on inflammatory and senescence markers in cartilage–subchondral bone explants from osteoarthritic patients

2011 ◽  
Vol 122 (5) ◽  
pp. 239-251 ◽  
Author(s):  
Victoria Clérigues ◽  
Maria Isabel Guillén ◽  
Francisco Gomar ◽  
Maria José Alcaraz
Keyword(s):  
Subchondral Bone ◽  
Transforming Growth Factor ◽  
Protoporphyrin Ix ◽  
High Mobility ◽  
Interleukin 1Β ◽  
Prostaglandin E ◽  
Galactosidase Activity ◽  
Human Telomerase Reverse Transcriptase ◽  
Markers Of Inflammation ◽  
Haem Oxygenase

IL (interleukin)-1β plays an important role in cartilage extracellular matrix degradation and bone resorption in OA (osteoarthritis) through the induction of degradative enzymes and pro-inflammatory mediators. In the present study, we have determined the consequences of HO-1 (haem oxygenase-1) induction on markers of inflammation and senescence in the functional unit cartilage–subchondral bone stimulated with IL-1β. Cartilage–subchondral bone specimens were obtained from the knees of osteoarthritic patients. Treatment with the HO-1 inducer CoPP (cobalt protoporphyrin IX) counteracted the stimulatory effects of IL-1β on IL-6, nitrite, PGE2 (prostaglandin E2), TGF (transforming growth factor) β2, TGFβ3 and osteocalcin. Immunohistochemical analyses indicated that CoPP treatment of explants down-regulated iNOS (inducible nitric oxide synthase), COX-2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E synthase-1) induced by IL-1β. In contrast, the expression of HMGB1 (high-mobility group box 1) was not significantly modified. In addition, CoPP decreased the expression of iNOS and mPGES-1 in cells isolated from the explants and stimulated with IL-1β, which was counteracted by an siRNA (small interfering RNA) specific for human HO-1. In isolated primary chondrocytes, we determined senescence-associated β-galactosidase activity and the expression of senescence markers by real-time PCR. We have found that HO-1 induction could regulate senescence markers in the presence of IL-1β and significantly affected telomerase expression, as well as β-galactosidase activity and hTERT (human telomerase reverse transcriptase) and p21 expression in chondrocytes. The findings of the present study support the view that HO-1 induction results in the down-regulation of inflammatory and senescence responses in OA articular tissues.

Haem oxygenase-1 induction reverses the actions of interleukin-1β on hypoxia-inducible transcription factors and human chondrocyte metabolism in hypoxia

2013 ◽  
Vol 125 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Victoria Clérigues ◽  
Christopher L. Murphy ◽  
Maria Isabel Guillén ◽  
Maria José Alcaraz
Keyword(s):  
Articular Chondrocytes ◽  
Protoporphyrin Ix ◽  
Interleukin 1Β ◽  
Protective Effects ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Cobalt Protoporphyrin ◽  
Haem Oxygenase ◽  
Oa Chondrocytes ◽  
Factor Α

HO-1 (haem oxygenase-1) catalyses the degradation of haem and possesses anti-inflammatory and cytoprotective properties. The role of inflammatory mediators in the pathogenesis of OA (osteoarthritis) is becoming increasingly appreciated. In the present study, we investigated the effects of HO-1 induction in OA and healthy HACs (human articular chondrocytes) in response to inflammatory cytokine IL-1 β (interleukin-1β) under hypoxic conditions. Hypoxia was investigated as it is a more physiological condition of the avascular cartilage. Hypoxic signalling is mediated by HIFs (hypoxia-inducible factors), of which there are two main isoforms, HIF-1α and HIF-2α. Normal and OA chondrocytes were stimulated with IL-1β. This cytokine suppresses HO-1 expression and exerts both catabolic and anti-anabolic effects, while increasing HIF-1α and suppressing HIF-2α protein levels in OA chondrocytes in hypoxia. Induction of HO-1 by CoPP (cobalt protoporphyrin IX) reversed these IL-1β actions. The hypoxia-induced anabolic pathway involving HIF-2α, SOX9 [SRY (sex determining region Y)-box 9] and COL2A1 (collagen type II α1) was suppressed by IL-1β, but importantly, levels were restored by HO-1 induction, which down-regulated TNFα (tumour necrosis factor α), MMP (matrix metalloproteinase) activity and MMP-13 protein levels. Depletion of HO-1 using siRNA (small interfering RNA) abolished the CoPP effects, further demonstrating that these were due to HO-1. The results of the present study reveal the different mechanisms by which HO-1 exerts protective effects on chondrocytes in physiological levels of hypoxia.

scholarly journals Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis

2018 ◽  
Vol 19 (11) ◽  
pp. 3647 ◽  
Author(s):  
Takako Takemiya ◽  
Marumi Kawakami ◽  
Chisen Takeuchi
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Vascular Endothelial Cells ◽  
Immunohistochemical Analysis ◽  
Interleukin 1Β ◽  
Prostaglandin E ◽  
Vascular Endothelial ◽  
Autoimmune Encephalomyelitis ◽  
Ep Receptor ◽  
Experimental Autoimmune

Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1−/−) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1−/− mice. In addition, endothelial interleukin-1β (IL-1β) production was significantly higher in wt mice than in mPGES-1−/− mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1–4) were expressed after EAE induction, and IL-1β was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1β production, modulating mPGES-1 induction in EAE.

scholarly journals Cardioprotective Role of Colchicine Against Inflammatory Injury in a Rat Model of Acute Myocardial Infarction

2018 ◽  
Vol 23 (5) ◽  
pp. 446-455 ◽  
Author(s):  
Oussama Bakhta ◽  
Simon Blanchard ◽  
Anne-Laure Guihot ◽  
Sophie Tamareille ◽  
Delphine Mirebeau-Prunier ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Ischemia Reperfusion ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Early Reperfusion ◽  
Beneficial Effects

Background: Inflammation plays a crucial role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. A clinical trial has recently reported a smaller infarct size in a cohort of patients with ST-segment elevation myocardial infarction (MI) treated with a short colchicine course. The mechanism underlying colchicine-induced cardioprotection in the early MI phase remains unclear. We hypothesized that a short pretreatment with colchicine could induce acute beneficial effects by protecting the heart against inflammation in myocardial I/R injury. Methods and Results: Rats were subjected to 40-minute left anterior descending coronary occlusion, followed by 120-minute reperfusion. Colchicine (0.3 mg/kg) or a vehicle was administered per os 24 hours and immediately before surgery. Infarct size was significantly reduced in the colchicine group (35.6% ± 3.0% vs 46.6% ± 3.3%, P < .05). The beneficial effects of colchicine were associated with an increased systemic interleukin-10 (IL-10) level and decreased cardiac transforming growth factor-β level. Interleukin-1β was found to increase in a “time of reperfusion”-dependent manner. Colchicine inhibited messenger RNA expression of caspase-1 and pro-IL-18. Interleukin-1β injected 10 minutes prior to myocardial ischemia induced greater infarct size (58.0% ± 2.0%, P < .05) as compared to the vehicle. Colchicine combined to IL-1β injection significantly decreased infarct size (47.1% ± 2.2%, P < .05) as compared to IL-1β alone, while colchicine alone exhibited a significantly more marked cardioprotective effect than the colchicine-IL-1β association. Conclusion: The cardioprotection induced by a short colchicine pretreatment was associated with an anti-inflammatory effect in the early reperfusion phase in our rat MI model.

scholarly journals Inhibition of Inflammatory Responses by Centella asiatica via Suppression of IRAK1-TAK1 in Mouse Macrophages

2020 ◽  
Vol 48 (05) ◽  
pp. 1103-1120
Author(s):  
Young-Chang Cho ◽  
Huong Lan Vuong ◽  
Jain Ha ◽  
Sewoong Lee ◽  
Jiyoung Park ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Centella Asiatica ◽  
Prostaglandin E ◽  
Methanol Fraction ◽  
Raw 264.7 Macrophages ◽  
Inflammatory Mechanism ◽  
Mouse Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Centella asiatica (L.) Urb. (C. asiatica) has been widely treated for inflammation-related diseases in China for thousands of years. While C. asiatica showed relevant effects as traditional medicine, the mechanism of C. asiatica suppressing inflammation has not been thoroughly investigated. Therefore, this study was conducted to reveal the anti-inflammatory mechanism of methanol fraction from C. asiatica (MCA) at the molecular level in murine macrophages. Levels of inflammation-related mediators were observed with treatment of MCA. MCA significantly suppressed nitric oxide production and iNOS expression in RAW 264.7 macrophages. Prostaglandin E2 production was alleviated by MCA via the downregulation of cyclooxygenase-2. MCA treatment also reduced pro-inflammatory tumor necrosis factor-[Formula: see text] and interleukin (IL)-6 levels. LPS/D-GalN-induced acute hepatitis in mouse was alleviated by MCA treatment. In addition, MCA decreased the phosphorylation of inhibitory [Formula: see text]B[Formula: see text] (I[Formula: see text]B[Formula: see text]) at Ser32/36 and thereby blocked I[Formula: see text]B[Formula: see text] degradation. TXY motif phosphorylation in the activation loops of mitogen-activated protein kinases (MAPKs) was also suppressed by MCA treatment. Further investigation revealed that MCA inhibited transforming growth factor-[Formula: see text]-activated kinase 1 (TAK1) phosphorylation and IL-1 receptor-associated kinase (IRAK1) degradation, the upstream kinases activating nuclear factor [Formula: see text]B and MAPKs. Taken together, MCA exhibited anti-inflammatory properties via the downregulation of IRAK1-TAK1 signaling pathways.

The effect of interleukin-1β and transforming growth factor β on cathepsin B activity in human articular chondrocytes

1994 ◽  
Vol 41 (S2) ◽  
pp. C198-C200 ◽  
Author(s):  
M. H. M. Meijers ◽  
C. M. Aisa ◽  
M. E. J. Billingham ◽  
R. G. G. Russell ◽  
R. A. D. Bunning
Keyword(s):  
Growth Factor ◽  
Cathepsin B ◽  
Transforming Growth Factor ◽  
Articular Chondrocytes ◽  
Transforming Growth Factor Β ◽  
Interleukin 1Β ◽  
Human Articular Chondrocytes

Effects of transforming growth factor-β on normal clonal bone cell populations

1991 ◽  
Vol 69 (2-3) ◽  
pp. 132-140 ◽  
Author(s):  
Rebecca Ber ◽  
Takao Kubota ◽  
Jaro Sodek ◽  
Jane E. Aubin
Keyword(s):  
Alkaline Phosphatase ◽  
Growth Factor ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Transforming Growth Factor Β ◽  
Prostaglandin E ◽  
Intracellular Camp ◽  
Type I

Although transforming growth factor-β (TGF-β) has been implicated in the local regulation of bone growth and remodelling, its specific effects on different subpopulations of bone cells have not been elucidated. Cells derived from bone are known to be heterogeneous and include both cells of different lineages and osteoblastic populations with different levels of expression of osteoblast-associated properties. Consequently, we have isolated clonal populations of bone cells to examine more precisely the effects of TGF-β on individual subpopulations. Several clonal populations were isolated by limiting dilution from cells derived from 21-day-old fetal rat calvaria. Two of these clones, RCA 11 and RCB 2, were used here. While the two clones responded similarly to parathyroid hormone (PTH) and isoproterenol (ISP) with increases in intracellular cAMP, prostaglandin E2 (PGE2) elicited a 10-fold higher response in RCB 2 cells compared with RCA 11. RCB 2 cells expressed a 10-fold higher alkaline phosphatase activity compared with RCA 11. Both clones synthesized a variety of bone matrix associated proteins, but only RCA 11 synthesized SPP-1 (osteopontin) constitutively. TGF-β stimulated growth of RCB 2 cells after 24 and 48 h of treatment, but had no effect on growth of RCA 11. TGF-β supported anchorage-independent growth of RCB 2 cells, but not that of RCA 11. A 24-h exposure to TGF-β decreased cAMP responsiveness to PTH and ISP slightly in both clones, but had no effect on PGE2 responses. Significant reductions in alkaline phosphatase activity were seen in both clones after 24- and 48-h treatments with TGF-β. Total protein synthesis as measured by [35S]methionine incorporation was stimulated significantly in both clones, but TGF-β selectively stimulated type I collagen compared with type III collagen. SPARC (osteonectin) and secreted phosphoprotein 1 (SPP-1; osteopontin) were stimulated by TGF-β in both RCA 11 and RCB 2 cells. These results indicate that individual clonal populations of cells within bone may be modulated differentially by TGF-β.Key words: transforming growth factor-β, osteoblasts, clonal cell lines, matrix synthesis.

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