ODN 2088
目录号 : GC66341
ODN 2088 是一种有效的 TLR3，TLR7 和 TLR9 抑制剂。ODN 2088 没有细胞毒性。ODN 2088 抑制 IFN-α 和 IL-6 的释放。
Cas No.:1146541-45-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ODN 2088 is a potent TLR3, TLR7 and TLR9 inhibitor. ODN 2088 shows no cytotoxic. ODN 2088 inhibits the release of IFN-α and IL-6[1][2][3].
ODN 2088 (0.01, 0.1, 1, 10 μM; 48 h) shows no cytotoxic for for human PBMCs[1].
ODN 2088 (0.01, 0.1, 1, 10 μM; 24 h) inhibits the release of IFN-α in CpG-ODN 2216 (3 μM) and TLR7-ligand RNA-ORN 22075 (5 μM) stimulated human PBMCs[1].
ODN 2088 (0.01, 0.1, 1, 10 μM; 48 h) hardly inhibits the IL-6 release stimulated with CpG-ODN 2006 (100 nM) but inhibits the IL-6 release stimulated with imiquimod (5 μg/ml) in human PBMCs[1].
ODN 2088 (0.1, 1, 10 μM; 24 h) hardly inhibits IL-6 release by B-cells stimulated with CpG-DNA 2006 (100 nM) but inhibits the IL-6 release by imiquimod (5 μg/ml) stimulated human B-cells[1].
ODN 2088 (1, 10 μM; 48 h) increases the expression of CD86 and HLA-DR in the absence of CpG-ODN 2006 or imiquimod in CD20+ B-cells[1].
ODN 2088 presumably impairs TLR9-induced signaling induces by CpG-ODNs by competitive binding to the C-terminal fragment of TLR9[1].
ODN 2088 (0.001, 0.01, 0.1, 1, 10 μM; 24 h) inhibits the TNF-α secretion in a dose-dependent manner in CpG-ODN 1826 (100 nM) stimulated BMDMs and shows weekly inhibits when stimulated by the TLR7-agonist imiquimod[3].
ODN 2088 (10 μM) stimulates B cells to proliferate[3].
Cell Cytotoxicity Assay[1]
| Cell Line: | Human PBMCs |
| Concentration: | 0.01, 0.1, 1, 10 μM |
| Incubation Time: | 48 h |
| Result: | Showed no cytotoxic for for human PBMCs. |
| Cas No. | 1146541-45-8 | SDF | Download SDF |
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
TLR9 agonist CpG ODN 2395 promotes the immune response against Leishmania donovani in obesity and undernutrition mice
Acta Trop 2023 Apr 6;242:106921.PMID:37030488DOI:10.1016/j.actatropica.2023.106921.
As important immunomodulators, CpG ODNs have broad application prospects in the treatment and prevention of leishmaniasis. In order to explore the immunomodulatory effect of CpG ODNs on mice infected with Leishmania parasites in different nutritional status, TLR9 agonist CpG ODN 2395 or TLR9 antagonist CpG ODN 2088 was injected into normal, obesity and undernutrition BALB/c mice infected with Leishmania donovani, respectively. Subsequently, spleen and liver parasite loads, spleen and liver immune gene expression, spleen T cell subsets proportion and PD-1 expression, serum lipids, serum cytokines, and anti-Leishmania antibodies were measured to assess the immune response of mice with different nutritional status. The results displayed that at the 8th week after infection, the spleen parasite load of obesity and undernutrition mice was significantly higher than that of normal mice, but the liver parasite load showed no statistical difference among the three groups. The treatment of CpG ODN 2395 or CpG ODN 2088 significantly reduced the spleen parasite load of obesity and undernutrition infected mice, but did not reduce that of normal infected mice. In obesity infected mice, CpG ODN 2395 promoted the up-regulation of TCR, ICOS and TLR4 in spleen, promoted the secretion of IFN-γ and anti-Leishmania total IgG and IgG1 antibodies, and increased the content of serum HDL-C. In undernutrition infected mice, CpG ODN 2395 promoted the up-regulation of spleen CD28 and TLR9, increased the proportion of spleen CD3+ T cells, and decreased the content of serum IL-10. Our results demonstrated that CpG ODN 2395 enhanced the immune response and clearance of Leishmania parasites in obesity and undernutrition mice, which might be used as a therapeutic agent for obesity and undernutrition leishmaniasis patients in the future.
Therapeutic Impact of ODN2088 to Block TLR9 Activity in Induced Liver Fibrosis Mice
Pak J Biol Sci 2021 Jan;24(1):122-131.PMID:33683038DOI:10.3923/pjbs.2021.122.131.
Background and objective: Liver fibrosis is the result of an excessive accumulation of extracellular matrix that develops when inflammation and chronic injury form scar tissue in the liver. Toll-like receptor 9 (TLR9) plays a central role in the innate immune response by recognition of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). This study aimed to show the therapeutic effects of TLR9 antagonist oligonucleotide (ODN) 2088 on liver fibrogenesis. Materials and methods: Mice were injected intraperitoneally with carbon tetrachloride (CCl4) or corn oil twice weekly for up to 8 weeks. Mice were also injected with CpG ODN 2088 (50 μg/20 g) daily for the last 4 weeks. At sacrifice, the serum level of liver enzyme activity was measured. Expression of pro-inflammatory and pro-fibrotic biomarkers was analyzed in liver tissue. Results: TLR9 antagonist, CpG ODN 2088, remarkably decreased the haptic inflammation and fibrosis during CCl4 administration. Treatment with CpG ODN 2088 resulted in reduced serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST). That was paralleled with inhibition in the production of intrahepatic inflammatory and fibrotic factors including collagen, α-Smooth Muscle Actin (SMA), Transforming Growth Factor-beta (TGF-β), interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α). Proliferation (Ki-67) and apoptosis (caspase-3) markers were highly suppressed after CpG ODN 2088 administration. Conclusion: Our results indicate that TLR9 antagonist, ODN 2088, showed protective effects against hepatics inflammation and fibrosis in the CCl4-induced fibrosis model. These observations suggest that ODN 2088 can be a potential therapeutic target for liver fibrosis treatment.
Toll-like receptor 9 antagonism modulates astrocyte function and preserves proximal axons following spinal cord injury
Brain Behav Immun 2019 Aug;80:328-343.PMID:30953770DOI:10.1016/j.bbi.2019.04.010.
Increasing evidence indicates that innate immune receptors play important, yet controversial, roles in traumatic central nervous system (CNS) injury. Despite many advances, the contributions of toll-like receptors (TLRs) to spinal cord injury (SCI) remain inadequately defined. We previously reported that a toll-like receptor 9 (TLR9) antagonist, oligodeoxynucleotide 2088 (ODN 2088), administered intrathecally, improves the functional and histopathological outcomes of SCI. However, the molecular and cellular changes that occur at the injury epicenter following ODN 2088 treatment are not completely understood. Following traumatic SCI, a glial scar, consisting primarily of proliferating reactive astrocytes, forms at the injury epicenter and assumes both beneficial and detrimental roles. Increased production of chondroitin sulfate proteoglycans (CSPGs) by reactive astrocytes inhibits the regeneration of injured axons. Astrocytes express TLR9, which can be activated by endogenous ligands released by damaged cells. It is not yet known how TLR9 antagonism modifies astrocyte function at the glial scar and how this affects axonal preservation or re-growth following SCI. The present studies were undertaken to address these issues. We report that in female mice sustaining a severe mid-thoracic (T8) contusion injury, the number of proliferating astrocytes in regions rostral and caudal to the lesion border increased significantly by 30- and 24-fold, respectively, compared to uninjured controls. Intrathecal ODN 2088 treatment significantly reduced the number of proliferating astrocytes by 60% in both regions. This effect appeared to be, at least partly, mediated through the direct actions of ODN 2088 on astrocytes, since the antagonist decreased proliferation in pure SC astrocyte cultures by preventing the activation of the Erk/MAPK signaling pathway. In addition, CSPG immunoreactivity at the lesion border was more pronounced in vehicle-treated injured mice compared to uninjured controls and was significantly reduced following administration of ODN 2088 to injured mice. Moreover, ODN 2088 significantly decreased astrocyte migration in an in vitro scratch-wound assay. Anterograde tracing and quantification of corticospinal tract (CST) axons in injured mice, indicated that ODN 2088 preserves proximal axons. Taken together, these findings suggest that ODN 2088 modifies the glial scar and creates a milieu that fosters axonal protection at the injury site.
Toll like receptor 9 antagonism modulates spinal cord neuronal function and survival: Direct versus astrocyte-mediated mechanisms
Brain Behav Immun 2016 Aug;56:310-24.PMID:27044334DOI:10.1016/j.bbi.2016.03.027.
Toll like receptors (TLRs) are expressed by cells of the immune system and mediate the host innate immune responses to pathogens. However, increasing evidence indicates that they are important contributors to central nervous system (CNS) function in health and in pathological conditions involving sterile inflammation. In agreement with this idea, we have previously shown that intrathecal administration of a TLR9 antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), ameliorates the outcomes of spinal cord injury (SCI). Although these earlier studies showed a marked effect of CpG ODN 2088 on inflammatory cells, the expression of TLR9 in spinal cord (SC) neurons and astrocytes suggested that the antagonist exerts additional effects through direct actions on these cells. The current study was undertaken to assess the direct effects of CpG ODN 2088 on SC neurons, astrocytes and astrocyte-neuron interactions, in vitro. We report, for the first time, that inhibition of TLR9 in cultured SC neurons alters their function and confers protection against kainic acid (KA)-induced excitotoxic death. Moreover, the TLR9 antagonist attenuated the KA-elicited endoplasmic reticulum (ER) stress response in neurons, in vitro. CpG ODN 2088 also reduced the transcript levels and release of chemokine (C-X-C) motif ligand 1 (CXCL1) and monocyte chemotactic protein 1 (MCP-1) by astrocytes and it diminished interleukin-6 (IL-6) release without affecting transcript levels in vitro. Conditioned medium (CM) of CpG ODN 2088-treated astroglial cultures decreased the viability of SC neurons compared to CM of vehicle-treated astrocytes. However, this toxicity was not observed when astrocytes were co-cultured with neurons. Although CpG ODN 2088 limited the survival-promoting effects of astroglia, it did not reduce neuronal viability compared to controls grown in the absence of astrocytes. We conclude that the TLR9 antagonist acts directly on both SC neurons and astrocytes. Neuronal TLR9 antagonism confers protection against excitotoxic death. It is likely that this neuroprotection is partly due to the attenuation of the ER stress response provoked by excitotoxicity. Although CpG ODN 2088 limits the supportive effects of astrocytes on neurons, it could potentially exert beneficial effects by decreasing the release of pro-inflammatory cytokines and chemokines by astroglia. These findings highlight the multiple roles of TLR9 in the SC and have implications for pathological conditions including SCI where excitotoxicity and neuroinflammation play a prominent role in neuronal degeneration.
Modulation of TLR9 response in a mouse model of herpes simplex virus encephalitis
Antiviral Res 2012 Dec;96(3):414-21.PMID:23043942DOI:10.1016/j.antiviral.2012.09.022.
We evaluated the effects of agonists and antagonist of toll-like receptor (TLR) 9 in comparison with a TLR3 agonist in a mouse model of herpes simplex virus type 1 (HSV-1) encephalitis (HSE). BALB/c mice received a single intranasal dose of either a TLR3 agonist (polyinosinic:polycytidylic acid; PIC), TLR9 agonists (oligodeoxynucleotides (ODNs) 1585, 1826 or 2395) or a TLR9 antagonist (ODN 2088), 1 day before and, for selected groups, 3 days after infection with HSV-1. Mice that received the pre-treatment with vehicle, PIC, ODNs 1585, 1826, 2395 and 2088 before infection had survival rates of 25%, 65%, 55%, 40%, 55% and 30%, respectively (P<0.05 for PIC and ODNs 1585 and 2395 versus vehicle). Infected mice subsequently treated with vehicle, ODNs 2395 and 2088 had survival rates of 9%, 0% and 30%, respectively (P<0.05, ODN 2088 versus other groups). The pre-treatment of mice with ODN 2395 reduced both the viral load (P<0.05 at day 5) and the production of CCL2, IL-6 and CCL5 at days 3, 4 and 5 (P<0.05 for IL-6 at day 3 and P<0.05 for CCL2 and CCL5 at day 4). Treatment of infected mice with ODN 2088 reduced the production of the same cytokines (P=0.07 for CCL2 and P=0.09 for IL-6 at day 5). Pre-treatment of mice with TLR9 agonists before infection reduces brain viral load and cytokine levels resulting in increased HSE survival rates. On the other hand, TLR9 antagonists can be helpful to control the inflammatory response that could be detrimental after infection.