Alleviation of Papain-Induced Osteoarthritis by Recombinant Human Endostatin via Downregulation of Matrix Metalloproteinase-13, Interleukin-1 and Interleukin-6 in Rats

2022 ◽  
Vol 12 (3) ◽  
pp. 625-629
Author(s):  
Chunpei Ou ◽  
Pengfei Chen ◽  
Jinqi Song ◽  
Xuefeng Deng ◽  
Feiqiang Chen ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Knee Joint ◽  
Interleukin 1 ◽  
The Elderly ◽  
Dependent Manner ◽  
Mankin Score ◽  
Recombinant Human Endostatin ◽  
Joint Cavity ◽  
Matrix Metalloproteinase 13 ◽  
Dose Dependent

Osteoarthritis (OA) is a degenerative disease of joints commonly occurring in the elderly and middleaged people. This study aimed to investigate the effect of recombinant human endostatin (rhEndo) on OA and the levels of MMP-13, IL-1 and IL-6 in the synovial fluid in osteoarthritis rats. OA models were made by injecting 4% papain into the knee joint cavity of rats once every three days for three times. The models were then injected subcutaneously with rhEndo and examined six weeks later for the Mankin scores and levels of MMP-13, IL-1 and IL-6 using ELISA. Compared with control, the Mankin score as well as the levels of IL-1, IL-6 and MMP-13 were significantly increased in the models (0.30 vs. 5.80, 1.12 vs. 12.84 pg/ mL, 12.22 vs. 43.82 pg/ mL and 0.23 vs. 26.31 ng/ mL). Following treatment with 4 mg/kg rhEndo, the Mankin score in model decreased to 0.90, meanwhile, the levels of IL-1, IL-6 and MMP-13 decreased significantly to 0.79 pg/ mL, 2.89 pg/mL and 1.17 ng/mL, respectively, in a dose dependent manner. Therefore, rhEndo can alleviate osteoarthritis by reducing MMP-13, IL-1 and IL-6 expression in rats.

scholarly journals Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor.

1992 ◽  
Vol 175 (4) ◽  
pp. 1139-1142 ◽  
Author(s):  
H R Alexander ◽  
G G Wong ◽  
G M Doherty ◽  
D J Venzon ◽  
D L Fraker ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Leukemia Inhibitory Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Inhibitory Factor ◽  
Dependent Manner ◽  
Lps Challenge ◽  
Differentiation Factor ◽  
Dose Dependent ◽  
Necrosis Factor

Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose-dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge.

scholarly journals Autocrine stimulation of interleukin 1 beta in acute myelogenous leukemia cells.

1987 ◽  
Vol 166 (5) ◽  
pp. 1597-1602 ◽  
Author(s):  
K Sakai ◽  
T Hattori ◽  
M Matsuoka ◽  
N Asou ◽  
S Yamamoto ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Interleukin 1 ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Acute Myelogenous ◽  
Autocrine Stimulation ◽  
Basal Proliferation ◽  
Culture Supernatants ◽  
Dose Dependent

A significant increase in CD25 antigen-positive cells by IL-1 was observed in cells of a patient with M7 acute myelogenous leukemia. Basal proliferation and expression of CD25 antigen by the M7 leukemic cells were inhibited by addition of anti-IL-1 beta antibody in a dose-dependent manner, but not by rabbit anti-IL-1 alpha antibody. Culture supernatants of these leukemic cells contained IL-1 activity, which was specifically inhibited by addition of anti-IL-1 beta antibody, and Northern blot analysis detected intracellular IL-1 beta mRNA. These results indicated that autocrine secretion of IL-1 beta was involved in proliferation of some myelogenous leukemic cells.

scholarly journals A redox-based mechanism for induction of interleukin-1 production by nitric oxide in a human colonic epithelial cell line (HT29-Cl.16E)

1996 ◽  
Vol 313 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Geneviève VALLETTE ◽  
Anne JARRY ◽  
Jean-Eric BRANKA ◽  
Christian L. LABOISSE
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cell ◽  
Cell Line ◽  
Interleukin 1 ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Colonic Epithelial Cell ◽  
Colonic Epithelial Cell Line ◽  
Dose Dependent ◽  
Human Colonic Epithelial Cell

We evaluated the effects of two NO donors, sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1), characterized by alternative redox states, i.e. nitrosonium ion (NO+) and nitric oxide (NO•) respectively, on intracellular interleukin-1 (IL-1) production, by a human colonic epithelial cell line (HT29-Cl.16E). SNP was able to induce intracellular IL-1α production up to 10 h incubation, in a dose-dependent manner. Several experiments provide evidence that the NO+ redox form, and not the free radical NO•, is implicated in the IL-1α production: (i) SIN-1, devoid of any NO+ character, led to a very weak IL-1 production as compared with SNP; (ii) the reductive action of a thiol such as cysteine on NO+ led to a dose-dependent increase in NO• concentration, measured as NO2-/NO3- accumulation, and to a large decrease in IL-1 production. Dibutyryl cGMP had no effect on IL-1 production, this finding supporting the concept that a cGMP-independent pathway is involved in the intracellular signalling of NO+. Together these results point out that NO, depending on its redox form, is able to modulate IL-1 production in cultured colonic epithelial cells.

Evidence that estrogen receptor β enhances MMP-13 promoter activity in HIG-82 cells and that this enhancement can be influenced by ligands and involves specific promoter sites

2007 ◽  
Vol 85 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Ting Lu ◽  
Yamini Achari ◽  
Jerome B. Rattner ◽  
David A. Hart
Keyword(s):  
Estrogen Receptor ◽  
Promoter Activity ◽  
Estrogen Receptor Β ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Connective Tissues ◽  
Matrix Metalloproteinase 13 ◽  
Promoter Construct ◽  
The Impact ◽  
Dose Dependent

Degradation of articular cartilage is characteristic of osteoarthritis, and matrix metalloproteinase-13 (MMP-13) has been implicated in this condition. Estrogen receptors (ERs) are present in connective tissues, indicating these tissues' potential responsiveness to estrogen. We based this study on the hypothesis that estrogen receptor β (ERβ) can modulate MMP-13 promoter activity. Transfection of cells with ERβ constructs led to the induction of the endogenous MMP-13 gene, as evidenced by increased mRNA levels. The results also indicated that MMP-13 promoter construct activity in the HIG-82 cell line significantly increased when ERβ was present, and that estrogen downregulated this response in a dose-dependent manner. ERβ was shown to enhance MMP-13 expression somewhat more strongly than ERα, and the impact of a number of selective ER modulators (tamoxifen, raloxifene, and ICI 182,780) on ERβ enhancement of promoter activity was found to be significantly less than that of estrogen. Furthermore, transcription regulatory sites in the MMP-13 promoter, specifically AP-1 and PEA-3, were shown to act in conjunction to mediate ERβ effects. Thus, ERβ likely influences MMP-13 promoter expression in normal and disease processes.

Effects of interleukin-1 infused into brain are antagonized by α-MSH in a dose-dependent manner

1991 ◽  
Vol 192 (1) ◽  
pp. 177-179 ◽  
Author(s):  
Jay M. Weiss ◽  
Syam K. Sundar ◽  
Mark A. Cierpial ◽  
James C. Ritchie
Keyword(s):  
Interleukin 1 ◽  
Dependent Manner ◽  
Dose Dependent

scholarly journals Inhibition of murine erythroid colony formation in vitro by interferon gamma and correction by interferon receptor immunoadhesin

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 911-915 ◽  
Author(s):  
RT Jr Means ◽  
SB Krantz ◽  
J Luna ◽  
SA Marsters ◽  
A Ashkenazi
Keyword(s):  
Animal Model ◽  
Interferon Gamma ◽  
Colony Formation ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Ifn Gamma ◽  
Dose Dependent

It has been previously reported that inhibition of human erythroid colony-forming units (CFU-E) in vitro by interleukin-1 (IL-1) is an indirect effect, occurring through the production of interferon gamma (IFN gamma). IFN gamma, in turn, inhibits CFU-E colony formation directly, and its inhibitory effect can be overcome by exposure to high concentrations of erythropoietin (EPO). To develop an in vitro animal model for investigating inhibition of erythropoiesis by IFN gamma, the effects of recombinant murine (rm) IFN gamma on highly purified CFU-E from the spleens of mice infected with the anemia strain of the Friend virus (FVA) were studied. rmIFN gamma inhibited CFU-E colony formation in a dose-dependent manner. This inhibition occurred with large (> or = 8 cell) colonies only; smaller colonies were not affected. The inhibitory effect was corrected to 72% of control by high EPO concentrations of 64 U/mL. Murine CFU-E were then cultured with rmIFN gamma in the presence of a soluble murine IFN gamma receptor fused to the hinge and Fc domains of the human IgG1 heavy chain (mIFN gamma R-IgG). Inhibition of CFU-E colony formation by rmIFN gamma (100 U/mL) was corrected by mIFN gamma R-IgG in a dose-dependent manner, with an approximate IC50 of 0.05 nmol/L, and complete or near complete correction at 0.5 nmol/L. Similarly, a human IFN gamma R-IgG greatly reduced the inhibitory effect of recombinant human IFN gamma on human CFU-E. These experiments provide an in vitro animal model for studying the inhibitory effects of IFN gamma on erythropoiesis and indicate that IFN gamma R-IgG may be a useful agent for reducing the toxicity of IFN gamma in vivo.

Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender

2000 ◽  
Vol 278 (4) ◽  
pp. R855-R862 ◽  
Author(s):  
Jane M. Daun ◽  
Richard W. Ball ◽  
Joseph G. Cannon
Keyword(s):  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Basal Secretion ◽  
Peripheral Blood Mononuclear ◽  
Age Related ◽  
Agonist And Antagonist ◽  
And Gender ◽  
Dose Dependent ◽  
Pituitary Adrenal Axis

Interleukin-1 (IL-1) is a primary mediator of inflammation that is regulated, in part, by the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine if gender- or age-related differences exist in the sensitivity of IL-1-producing cells to hydrocortisone. Peripheral blood mononuclear cells (PBMC) isolated from men and women (21–77 yr old) were incubated with hydrocortisone (0, 50, 100, 500, or 1,000 ng/ml) with or without lipopolysaccharide (LPS). Secretion of IL-1β and IL-1 receptor antagonist was inhibited in a dose-dependent manner ( P = 0.001) without age- or gender-related differences. Hydrocortisone decreased soluble IL-1 receptor type II (sIL-1RII) secretion by unstimulated cells ( P = 0.0001), but it increased secretion by LPS-stimulated cells ( P = 0.0001) in all groups. Unstimulated cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women ( P= 0.011). Compared with men, PBMCs from women were less responsive to hydrocortisone inhibition of sIL-1RII secretion, regardless of age ( P = 0.001), and compared with the follicular phase, sIL-1RII secretion was lower in the luteal phase of the menstrual cycle ( P < 0.05). These data indicate that basal secretion and glucocorticoid modulation of sIL-1RII secretion by cultured PBMCs are gender dependent. Moreover, glucocorticoid influences on sIL-1RII secretion depend on the presence or absence of gram-negative bacterial toxins.

scholarly journals Extracts ofCistanche deserticolaCan Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Ke Zhang ◽  
Xu Ma ◽  
Wenjun He ◽  
Haixia Li ◽  
Shuyan Han ◽  
...  
Keyword(s):  
T Cells ◽  
Life Span ◽  
Dietary Supplementation ◽  
The Elderly ◽  
Dependent Manner ◽  
Cistanche Deserticola ◽  
Kaplan Meier ◽  
Extend Life Span ◽  
Dose Dependent ◽  
Senescence Accelerated Mouse

The senescence accelerated mouse prone 8 substrain (SAM-P8), widely accepted as an animal model for studying aging and antiaging drugs, was used to examine the effects of dietary supplementation with extracts ofCistanche deserticola(ECD) which has been used extensively in traditional Chinese medicine because of its perceived ability to promote immune function in the elderly. Eight-month-old male SAM-P8 mice were treated with ECD by daily oral administrations for 4 weeks. The results showed that dietary supplementation of 150 mg/kg and 450 mg/kg of ECD could extend the life span measured by Kaplan-Meier survival analysis in dose-dependent manner. Dietary supplementation of SAM-P8 mice for 4 weeks with 100, 500, and 2500 mg/kg of ECD was shown to result in significant increases in both naive T and natural killer cells in blood and spleen cell populations. In contrast, peripheral memory T cells and proinflammatory cytokine, IL-6 in serum, were substantially decreased in the mice that ingested 100 and 500 mg/kg of ECD daily. Additionally, Sca-1 positive cells, the recognized progenitors of peripheral naive T cells, were restored in parallel. Our results provide clear experimental support for long standing clinical observational studies showing thatCistanche deserticolapossesses significant effects in extending life span and suggest this is achieved by antagonizing immunosenescence.

scholarly journals Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1476-1484 ◽  
Author(s):  
Z Estrov ◽  
R Kurzrock ◽  
M Wetzler ◽  
H Kantarjian ◽  
M Blake ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Chronic Myelogenous Leukemia ◽  
Interleukin 1 ◽  
Colony Growth ◽  
Myelogenous Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Density ◽  
Cell Fractionation ◽  
Dependent Manner ◽  
Dose Dependent

Abstract In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony- stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the “autonomous” colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder.

ACTH response in rats during biphasic fever induced by interleukin-1

1991 ◽  
Vol 261 (5) ◽  
pp. R1104-R1108 ◽  
Author(s):  
T. Watanabe ◽  
A. Morimoto ◽  
N. Murakami
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Potent Inhibitor ◽  
Interleukin 1 ◽  
High Dose ◽  
Dependent Manner ◽  
Interleukin 1 Beta ◽  
Beta 2 ◽  
High Concentrations ◽  
Dose Dependent ◽  
The Brain

Injection of a low concentration (0.3 micrograms/kg iv) of interleukin-1 beta (IL-1 beta) produced monophasic fever, but high concentrations (15 micrograms/kg iv) produced biphasic fever in rats. Treatment with IL-1 beta caused dose-dependent rises in the plasma concentration of adrenocorticotropic hormone (ACTH) 30 min after injection. Moreover, significant increases in plasma levels of ACTH were observed 90 and 180 min after injection of the high dose of IL-1 beta. ACTH response induced by IL-1 beta (15 micrograms/kg iv) was suppressed by pretreatment with injection of indomethacin (Indo), a potent inhibitor of prostaglandin (PG) synthesis, in a dose-dependent manner (1 and 10 mg/kg iv). Also, biphasic fever induced by the high dose of IL-1 beta was completely abolished by pretreatment with the intravenous injection of Indo. Intracerebroventricular (icv) injection of Indo (50 micrograms) did not affect febrile and ACTH responses induced by intravenous IL-1 beta, whereas those responses induced by IL-1 beta (2 ng icv) were significantly suppressed by injection of Indo (50 micrograms icv). Although it is possible that intracerebroventricular Indo does not reach the site of intravenous IL-1 beta action within the brain, these results suggest that in rats febrile and ACTH responses induced by intravenous IL-1 beta are caused by IL-1 beta-acting structures outside the blood-brain barrier. It is likely that these structures subsequently synthesize and release PGE2, which in turn induces ACTH and febrile responses in rats.

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