Adenovirus-mediated transduction with Histone Deacetylase 4 ameliorates disease progression in an osteoarthritis rat model.


BACKGROUND:Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. METHODS:Rat chondrocytes were infected with Ad-GFP or Ad-HDAC4-GFP for 48 h, stimulated with interleukin-1β (IL-1β, 10 ng/mL) for 24 h, and then harvested for RT-qPCR. Male Sprague-Dawley rats in 3 groups were given anterior cruciate ligament transection (ACLT) or sham operation, and knee injections with different adenovirus (Ad) vectors at 48 h after surgery and every 3 weeks thereafter: ACLT+Ad-GFP (n = 17); ACLT+Ad-HDAC4-GFP (n = 20); and sham+Ad-GFP (n = 15). Three ACLT-Ad-HDAC4-GFP rats were sacrificed at different times to examine the expression of HDAC4. Two ACLT-Ad-GFP rats and two ACLT-Ad-HDAC4-GFP rats were euthanized at week-2; articular cartilage was harvested and expression of HDAC4 was determined by RT-qPCR. All other rats were euthanized at week-8. Cartilage damage and OA progression was assessed using radiography, fluorescence molecular tomography (FMT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. RESULTS:Overexpression of HDAC4 in chondrocytes stimulated by IL-1β reduced the levels of Runx-2, MMP-13, and Collagen X, but increased the levels of Collagen II and Aggrecan. Upregulation of HDAC4 reduced osteophyte formation and cartilage damage, and increased articular cartilage anabolism. CONCLUSION:HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA. Upregulation of HDAC4 may provide chondroprotection in OA patients.


Int Immunopharmacol


Gu XD,Wei L,Li PC,Che XD,Zhao RP,Han PF,Lu JG,Wei XC




Has Abstract


2019-10-01 00:00:00












  • Stimulatory effect of a pectic polysaccharide from a medicinal herb, the roots of Bupleurum falcatum L., on G-CSF secretion from intestinal epithelial cells.

    abstract::The inner surface of the intestinal tract possesses a large area of mucosal membranes, and the intestinal epithelial cells exist at the interface between an antigen-rich lumen and a lymphocyte-rich lamina propria. The crosstalk that occurs between these compartments serves to maintain intestinal homeostasis, and the c...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Matsumoto T,Moriya M,Sakurai MH,Kiyohara H,Tabuchi Y,Yamada H

    更新日期:2008-04-01 00:00:00

  • Indirubin-3'-monoxime prevents aberrant activation of GSK-3β/NF-κB and alleviates high fat-high fructose induced Aβ-aggregation, gliosis and apoptosis in mice brain.

    abstract::Deciphering the molecular mechanisms of amyloid pathology and glial cell-mediated neuroinflammation, offers a novel avenue for therapeutic intervention against neurodegeneration. Recent findings demonstrate a crucial link between activation of glycogen synthase kinase-3β (GSK-3β), amyloid deposition and a neuroinflamm...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Sathiya Priya C,Vidhya R,Kalpana K,Anuradha CV

    更新日期:2019-05-01 00:00:00

  • Chromatin remodeling complex in Treg function.

    abstract::Regulatory T cells (Treg), formerly known as suppressor T cells, are essential for maintaining self-tolerance as well as immune homeostasis. Lack of Treg or normal function of Treg often leads to lymphoproliferative syndrome and autoimmunity in human and mouse. The chromatin remodeling BAF complex regulates gene expre...

    journal_title:International immunopharmacology

    pub_type: 杂志文章,评审


    authors: Jani A,Chi T,Wan YY

    更新日期:2009-05-01 00:00:00

  • The relationship between pro-resorptive inflammatory cytokines and the effect of high dose vitamin D supplementation on their circulating concentrations.

    abstract::Inflammatory/pro-resorptive cytokines and chemokines form part of a complex inter-dependent network and may be influenced by vitamin D. We investigated their inter-relationship and the effect of a loading dose of vitamin D. We measured plasma concentrations of an array of cytokines including tumour necrosis factor-alp...

    journal_title:International immunopharmacology

    pub_type: 临床试验,杂志文章


    authors: Karim Y,Turner C,Dalton N,Roplekar R,Sankaralingam A,Ewang M,Fogelman I,Hampson G

    更新日期:2013-11-01 00:00:00

  • Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response.

    abstract::The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignan...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: De Costa AM,Justis DN,Schuyler CA,Young MR

    更新日期:2012-07-01 00:00:00

  • Nordihydroguaiaretic acid (NDGA) and α-mangostin inhibit the growth of Mycobacterium tuberculosis by inducing autophagy.

    abstract::Tuberculosis (TB) remains as a global health problem. The prevalence of this infection is related to the association with other diseases, such as HIV, neglect treatment and misuse of antibiotics. Hence, the identification of new drugs is required to eradicate TB. Possible alternatives to existing antibiotics include p...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Guzmán-Beltrán S,Rubio-Badillo MÁ,Juárez E,Hernández-Sánchez F,Torres M

    更新日期:2016-02-01 00:00:00

  • A novel chrysin thiazole derivative polarizes macrophages to an M1 phenotype via targeting TLR4.

    abstract::Tumor-associated macrophages (TAMs) are an important cause of tumorigenesis and tumor development. M2 macrophages can promote tumor growth while M1 macrophages kill tumor cells, therefore, polarizing macrophages to achieve a functional M1 phenotype could effectively play its anti-tumor role. In the current study, we s...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Feng X,Yu W,Cao L,Meng F,Cong M

    更新日期:2020-11-01 00:00:00

  • The therapeutic potential of microbial proteasome inhibitors.

    abstract::The proteasome influences cellular homeostasis through the degradation of regulatory proteins, many of which are also involved in disease pathogenesis. In particular, numerous regulatory proteins associated with tumor growth, such as cyclins, cyclin-dependent kinase inhibitors, tumor suppressors, and NF-κB inhibitors ...

    journal_title:International immunopharmacology

    pub_type: 杂志文章,评审


    authors: Momose I,Kawada M

    更新日期:2016-08-01 00:00:00

  • Profiles of immune cell infiltration and their clinical significance in head and neck squamous cell carcinoma.

    abstract::It is well established that there exist comprehensive interactions between tumor immunology and tumor biology. Tumor-infiltrating immune cells (TIICs) have been appealing therapeutic targets due to their significance in regulating cancer progression. The purpose of this study was to illustrate the comprehensive landsc...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Jin Y,Qin X

    更新日期:2020-03-04 00:00:00

  • Aspirin modified dendritic cells are potent inducers of allo-specific regulatory T-cells.

    abstract::Salicylic acid (aspirin) is a widely used pharmacological agent with immunodmodulatory properties. Dendritic cells are key regulators of the immune response, and are capable of inducing hyporesponsiveness and regulatory activity in CD4+ T-cells. We have demonstrated that aspirin-treated dendritic cells are effective a...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Buckland M,Jago C,Fazekesova H,George A,Lechler R,Lombardi G

    更新日期:2006-12-20 00:00:00

  • Lactobacillus plantarum reduces Streptococcus pyogenes virulence by modulating the IL-17, IL-23 and Toll-like receptor 2/4 expressions in human epithelial cells.

    abstract::Streptococcus pyogenes is a common colonizer of the mucosal layers in the mouth, nose, and pharynx but it is also a major Gram-positive human pathogen that causes infections ranging from pharyngitis to severe systemic diseases. The lactobacilli colonize the oral tracts and are known to protect against colonization by ...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Rizzo A,Losacco A,Carratelli CR,Domenico MD,Bevilacqua N

    更新日期:2013-10-01 00:00:00

  • Mogroside IVE attenuates experimental liver fibrosis in mice and inhibits HSC activation through downregulating TLR4-mediated pathways.

    abstract::Liver fibrosis has been emphasized as a serious threat to human health. There is currently no effective clinical drug treatment. Although mogrosides (MGs) have extensive pharmacological effects with minimal toxicity, their effects on liver function, inflammation, matrix metalloproteinases and hepatic stellate cell (HS...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Cao F,Zhang Y,Li W,Shimizu K,Xie H,Zhang C

    更新日期:2018-02-01 00:00:00

  • Mechanistic target of rapamycin-mediated autophagy is involved in the alleviation of lipopolysaccharide-induced acute lung injury in rats.

    abstract::Acute lung injury (ALI) is a complex clinical syndrome with high morbidity and mortality rates. Autophagy is an adaptive process that plays a complex role in ALI. The aim of this study was to investigate the effects of autophagy on lipopolysaccharide (LPS)-induced lung injury by establishing a rat ALI model and to fur...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Qin L,Li M,Tan HL,Yang HX,Li SD,Luan ZX,Chen YF,Yang MH

    更新日期:2020-01-01 00:00:00

  • Immune stimulation improves endocrine and neural fetal outcomes in a model of maternofetal thyrotoxicosis.

    abstract::The potentiation of the immune system in pregnant rats was performed with Complete Freund's Adjuvant [CFA; 20μl, subcutaneous at gestation day (GD) 18] in experimentally-induced hyperthyroidism by Levo-thyroxine (L-T4; 10μg/100g of b.w., intraperitoneal from GD 2 to 17). The potential effects on the fetal neuroendocri...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Ahmed RG,Abdel-Latif M,Mahdi EA,El-Nesr KA

    更新日期:2015-12-01 00:00:00

  • Molecular mechanisms of IgE mediated food allergy.

    abstract::The purpose of this review is to collate current knowledge and recent advances in molecular mechanism behind the immediate type hypersensitivity of foods. Food allergy is a growing concern of human health in developed as well as developing countries now days. Food allergic reactions are mostly IgE mediated and also kn...

    journal_title:International immunopharmacology

    pub_type: 杂志文章,评审


    authors: Kumar S,Verma AK,Das M,Dwivedi PD

    更新日期:2012-08-01 00:00:00

  • Anti-arthritic effects of chlorogenic acid in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model.

    abstract::Cartilage degradation is one of the pathological changes of osteoarthritis (OA), and accumulating evidence suggests an excess of matrix metalloproteinases (MMPs) plays a role in this cartilage breakdown. Here, we investigated the effects of chlorogenic acid (CGA) on the mRNA and protein expression of MMPs in interleuk...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Chen WP,Tang JL,Bao JP,Hu PF,Shi ZL,Wu LD

    更新日期:2011-01-01 00:00:00

  • Molecular mechanisms in lipopolysaccharide-induced pulmonary endothelial barrier dysfunction.

    abstract::The confluent pulmonary endothelium plays an important role as a semi-permeable barrier between the vascular space of blood vessels and the underlying tissues, and it contributes to the maintenance of circulatory fluid homeostasis. Pulmonary endothelial barrier dysfunction is a pivotal early step in the development of...

    journal_title:International immunopharmacology

    pub_type: 杂志文章,评审


    authors: Liu H,Yu X,Yu S,Kou J

    更新日期:2015-12-01 00:00:00

  • Identification and verification of an immune-related lncRNA signature for predicting the prognosis of patients with bladder cancer.

    abstract:BACKGROUND:Recent studies have revealed the significant roles of immune-related long noncoding RNAs (lncRNAs) in cancer development and progression. The identification of biomarkers that contribute to early detection and risk stratification provides significant benefits for bladder cancer (BC) patients. The current stu...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Wang J,Shen C,Dong D,Zhong X,Wang Y,Yang X

    更新日期:2021-01-01 00:00:00

  • Risperidone modulates the cytokine and chemokine release of dendritic cells and induces TNF-α-directed cell apoptosis in neutrophils.

    abstract::Antipsychotic drugs (APDs) that bind mainly to the dopamine D2 receptor or the type II 5-HT receptor have been used to ease the symptoms of schizophrenia. Several studies have reported that APDs can also regulate the immune response. Dendritic cells (DCs) are the major antigen-presenting cells in the immune system. DC...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Chen ML,Tsai TC,Wang LK,Lin YY,Tsai YM,Lee MC,Tsai FM

    更新日期:2012-01-01 00:00:00

  • Stimulatory effect of antidepressants on the production of IL-6.

    abstract::A body of evidence indicates that the therapeutic activity of antidepressants is connected with their modulatory effect on the inflammatory response system and cell-mediated immunity. The present study was carried out to examine the effects of antidepressant agents, such as imipramne, venlafaxine, l-5-hydroxytryptopha...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Kubera M,Kenis G,Bosmans E,Kajta M,Basta-Kaim A,Scharpe S,Budziszewska B,Maes M

    更新日期:2004-02-01 00:00:00

  • Differential alteration of functions of rat peritoneal macrophages responsive to endogenous opioid peptide endomorphin-1.

    abstract::Endomorphin-1 is a recently isolated endogenous opioid peptide, and potent and selective high affinity mu-opioid receptor agonist. We evaluate the role of endomorphin-1 on macrophage functions. Endomorphin-1 potentiated macrophage adhesion and the expression of adhesion molecule Mac-1 on macrophages. However, endomorp...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Inui Y,Azuma Y,Ohura K

    更新日期:2002-07-01 00:00:00

  • Functional alterations in CD11b(+)Gr-1(+) cells in mice injected with allogeneic tumor cells and treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure results in an increased percentage of CD11b(+) (Mac-1(+)) cells in the spleens of mice challenged with P815 tumor cells, coincident with a failure of the mice to generate allospecific CD8(+) CTL activity. Since CD11b(+)Gr-1(+) myeloid suppressor cells (MSC) have been...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Choi JY,Oughton JA,Kerkvliet NI

    更新日期:2003-04-01 00:00:00

  • Glycyrrhizin regulates CD4+T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathway.

    abstract::The aims of this study were to elucidate the immunomodulatory effects of glycyrrhizin (GL) on CD4(+)T cell responses during liver fibrogenesis. To obtain in vivo evidence about the effects of GL on CD4(+)T cells in livers and spleens of concanavalin A (ConA)-induced mouse model, mice were administrated with ConA toget...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Tu CT,Li J,Wang FP,Li L,Wang JY,Jiang W

    更新日期:2012-12-01 00:00:00

  • Different roles of bortezomib and ONX 0914 in acute kidney injury.

    abstract::Proteasome inhibitor bortezomib offers one more option for acute or chronic antibody-mediated rejection after kidney transplantation, but aggravated acute kidney injury (AKI) in some cases early after surgery using bortezomib bring new problem. Here, we evaluated the effects of bortezomib and ONX-0914 on renal tubule ...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Zhang XZ,Han F,Ding CG,Dou M,Wang YX,Xue WJ,Ding XM,Zheng J,Xu CX,Tian PX

    更新日期:2020-03-03 00:00:00

  • Interleukin-10 delivered by mesenchymal stem cells attenuates experimental autoimmune myocarditis.

    abstract:BACKGROUNDS:Autoimmune myocarditis is characterized by over-activated immune system attacking the cardiomyocytes, resulting in heart function decline. In the current study, we investigated the therapeutic advantages of delivering Interleukin-10 (IL-10) by mesenchymal stem cells (MSCs), both of which had immune suppress...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Shao M,Wang D,Zhou Y,Du K,Liu W

    更新日期:2020-04-01 00:00:00

  • Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation.

    abstract::IL-6 is involved in inflammation and a therapeutic target. 0.1% of Danish blood donors have nanomolar plasma concentrations of polyclonal, picomolar affinity and in vitro as well as in vivo neutralizing IgG autoantibodies to IL-6 (aAb-IL-6). Such donors are assumed to be severely IL-6 deficient; yet they appear health...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Galle P,Jensen L,Andersson C,Cuzzocrea S,Di Paola R,Nicoletti F,Svenson M,Bendtzen K,Thomsen AR,Hansen MB

    更新日期:2007-12-15 00:00:00

  • Anti-tumor and immunomodulatory activities of an exopolysaccharide from Rhizopus nigricans on CT26 tumor-bearing mice.

    abstract::This study was aimed to investigate the anti-tumor and immunomodulatory activities of an exopolysaccharide (EPS) from Rhizopus nigricans. Our results showed EPS could significantly inhibit the tumor growth and increase the immune organs index of CT26 tumor-bearing mice. EPS treatment increased the productions of inter...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Zhu L,Cao J,Chen G,Xu Y,Lu J,Fang F,Chen K

    更新日期:2016-07-01 00:00:00

  • MicroRNA-204-GSDMD interaction regulates pyroptosis of fibroblast-like synoviocytes in ankylosing spondylitis.

    abstract:OBJECTIVE:Ankylosing spondylitis (AS) is a disease characterized by inflammation of the sacroiliac joint and the attachment point of the spine. This study aimed to investigate the effect of microRNA (miR)-204-targeted GSDMD on fibroblast-like synoviocytes (FLSs) in AS. METHODS:miR-204, GSDMD, pyrolysis-related genes (...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Gu G,Huo Y,Xu G,Li L,Yu J,Sheng L,Yin Z

    更新日期:2021-02-01 00:00:00

  • Altered expression of microRNAs may predict therapeutic response in rheumatoid arthritis patients.

    abstract:BACKGROUND:Epigenetic alternations of microRNAs (miRNAs) can contribute to the pathogenesis and progression of rheumatoid arthritis (RA). This study aimed to measure the expression level of peripheral blood miRNAs, as well as their target mRNAs, in RA patients and healthy controls (HCs), and to evaluate the potential o...

    journal_title:International immunopharmacology

    pub_type: 杂志文章


    authors: Rezaeepoor M,Pourjafar M,Tahamoli-Roudsari A,Basiri Z,Hajilooi M,Solgi G

    更新日期:2020-06-01 00:00:00

  • Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review.

    abstract::Many herbal products are now used as remedies to treat various infectious and non-infectious conditions. Even though the use of herbs and natural products is much more evident in the Eastern world, their use in Western cultures is continuously increasing. Although the immunomodulatory effects of some herbs have been e...

    journal_title:International immunopharmacology

    pub_type: 杂志文章,评审


    authors: Majdalawieh AF,Fayyad MW

    更新日期:2015-09-01 00:00:00