Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll–LikeReceptor4 Pathway in LPS-Induced RAW 264.7 Cells
Inflammation is a biological response to the immune system to defend the body of negative stimulation. However, the excessive inflammatory response can damage host tissues and pose serious threats. Exopolysaccharide (EPS), one of the postbiotics, is secreted with respect to lactic acid bacteria. Although many studies have described the beneficial effects of EPS, such as its anti-inflammatory and antioxidant effects, its underlying mechanisms have remained poorly understood. Thus, we have identified that the EPS obtained from Lactobacillus Plantarum L-14 were homogeneous polysaccharide composed mainly of glucose. To examine these anti-inflammatory effects, an inflammatory response has been induced by the administration of lipopolysaccharide (LPS) with pretreated Mouse 264.7 mouse and EPS macrophage cells.
The anti-inflammatory effects of EPAs have been identified by analyzing changes in inflammatory markers at the molecular level. We demonstrate here that the preflammatory mediators of the EPS have removed EPS, such as cyclooxygenase-2, interleukin-6, the tumor-α-α and interleukin-1β factor and decreased the expression of An inducible nitric oxide synthase known to cause an oxidative constraint. It has also been confirmed that the EPA had anti-inflammatory effects by blocking the LPS interaction with a toll (TLR4) receptor (TLR4), as demonstrated using TAK-242 TLR4 inhibitor. In addition, we found that the EPS itself could delete the expression of TLR4. Therefore, our data suggest that EPAs can be a potential target for the development of natural drug derivative drugs to treat inflammatory diseases related to TLR4.
The preconditioning of mycophenolate Mofofetil protects the liver from the mouse against the ischemia / lesion of the ePaction in the wild type and <em> toll </ em> – <em> like </ em> <em> receiver </ em> <em> 4 </ em> knockout and mouse
Context: Mycophenolate Mofetil (MMF), Immunosuppressive drug, exerts anti-inflammatory effects on the organs during an injury to ischemia / reperfusion (I / R). However, the exact function of MMF in a hepatic injury I / R remains largely unknown. The purpose of this study was to explore the role and the potential mechanism of MMF protection in Hepatic Injuries I / R.
Methods: Male Wild Type (WT) and TLR4 Knockout (KO) The mice were injected intraperitoneally with MMF or normal saline. The animals suffered 90 minutes of partial hepatic ischemia, followed by 1, 6 or 24 hours of reperfusion. Hepatic Histology, serum amiotransferase, inflammatory cytokines, apoptosis of hepatocytes and hepatocyte autophagia were examined to evaluate liver injuries.
Results: The treatment with MMF has decreased considerably of a hepatic injury I / R, as indicated by a reduction in serum aminotransferase levels, suzuki scores and the general degree of necrosis. MMF processing has significantly inhibited TLR4 activation. The MMF administration has also significantly inhibited the activation of the NF-KB channel and the expression of pro-inflammatory cytokines. In the mice TLR4 KO, MMF has always exerted protection against hepatic injuries I / R. The MMF treatment has inhibited the apoptosis of the hepatocyte, as indicated by the reduced tunnel coloring and reduces the accumulation of clevered caspase. 3. In addition, MMF can induce autophagy and increase the self-phage flow before and after hepatic reperfusion by increasing the expression of LC3-II, P62 and Beclin-1. The induction of autophagy by MMF treatment can be linked to TLR4 activation.
Conclusions: Our results indicate that MMF processing improves hepatic injury I / A. The action mechanism probably involves MMF’s ability to reduce apoptosis and inflammatory response while inducing autophagy.
Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll–LikeReceptor4 Pathway in LPS-Induced RAW 264.7 Cells
Statins inhibit <em> toll </ em> – <em> like </ em> <em> </ em> <em> 4 </ em> medicated growth of adenocarcinoma cells of human esophagus
Background: Oesophageal adenocarcinoma (EAC) is a deadly malignancy with a bad prognosis. Pharmacological inhibitors of inflammation, such as statins, have been demonstrated to reduce the risk of development and progression of esophagus cancer, but the mechanism of this protection is not clear. The objective of this study was to elucidate the effect of statins on the toll receptor of the mediation proliferation of the human face and to identify the mechanism responsible for these observed effects.
Methods: Human EAC cells (OE33 and FLO1) have been treated with simvastatin or atorvastatin to increase doses and periods of time. The expression of the till type 4 (TLR4) has been evaluated. The cells were pretreated with the statin followed by lipopolysaccharide (LPS). Cell proliferation and the expression of signaling proteins have been evaluated. FLO1 cells were injected into the naked mouse side. The mice received intraperitoneal injections of the simvastatin, atorvastatin or the control solution and the volume of the tumor was measured.
Results: OE33 and FLO1 cells have demonstrated reduced expression of TLR4 after treatment with simvastatin or atorvastatin for 8 h (p <0.05). The increased proliferation of the LPS, while pretreatment with the statin abolished this response (p <0.05). Statins decreased the expression and activation of LPS-induced signaling proteins, including MyD88, Traf6, AKT and NF-κB (p <0.05). Mice receiving statin daily injections have demonstrated smaller tumors than control mice (p <0.001 to day 33).
Conclusions: The treatment of EAC cells with simvastatin or atorvastatin decreases the mediation proliferation of the TLR4 and the growth of the Vivo tumor. The decrease in the expression of TLR4 and a subsequent reduction of the dependent signaling of MyD88 could be a mechanism by which statins act to reduce tumor growth rates.
Description: IL-17 binds to IL-17 receptors (IL-17 R), which share no homology with any known family of receptors. While the expression of IL-17 is restricted to activated T cells, IL-17 R mRNA exhibits a broad tissue distribution, and has been detected in virtually all cells and tissues tested. The amino acid sequence of human IL-17 R is 69% identical to mouse IL-17 R.
Description: IL-21 R, also called NILR (novel interleukin receptor) is a type I cytokine receptor with four conserved cysteine residues and an extracellular WSXWS motif. It is most closely related to IL-2 R beta and IL-9 R alpha. Mouse and human IL-21 R share 62% amino acid identity. IL-21 R is expressed on lymphoid tissues, peripheral B cells, and cell lines of T, B and natural killer cell lineage. IL-21 mediated signaling requires the common gamma chain in addition to IL-21 R.
Description: IL-17B receptor (IL-17B R), also known as IL-17Rh1, IL-17ER and EVI27, is a 502 amino acid (aa) type I membrane protein with a 17 aa signal peptide, a 275 aa extracellular domain, a 21 aa transmembrane domain and a 189 aa cytoplasmic tail. By alternative splicing, a secreted variant of IL-17B R has also been identified.
Description: IL-2 Receptor beta in frozen human lymph node. View IL-2 R beta IHC images. IL-2 R beta is a 551 amino acid (aa) precursor type I membrane protein with a 26 aa signal peptide, a 214 aa extracellular region, a 25 aa transmembrane region and a 286 aa cytoplasmic domain. IL-2 R beta binds IL-2 as a part of the IL-2 R alpha/IL-2 R beta/common gamma chain complex.
Description: IL-10 mediates its biological activities via binding to a heteromeric complex of two distinct type II cytokine receptor subunits, the ligand binding subunit IL-10 R alpha (IL-10 R1) and the signal-transducing accessory subunit IL-10 R beta (IL-10 R2). IL-10 R alpha is specific for IL-10 and expressed by most hemopoietic cells. IL-10 R beta is a widely expressed shared subunit for IL-10, IL-22, IL-26 and the IFNl proteins IL-28A, IL-28B and IL-29.
Description: The functional IL-18 receptor complex is composed of two subunits designated IL-18 R alpha (also termed IL-1 R5 and IL-1 Rrp) and IL-18 R beta (also termed IL-1 R7 and AcPL). Both IL-18 R alpha and IL-18 R beta belong to the IL-1 receptor family. Although IL-18 R alpha by itself binds IL-18 with low-affinity and IL-18 R beta does not bind IL-18 in vitro, co-expression of IL-18 R alpha and IL-18 R beta is required for high-affinity binding and IL-18 responsiveness. IL-18 R is widely expressed in numerous tissues including spleen, thymus, leukocyte, liver, lung, heart, small and large intestine, prostate and placenta. It is not expressed in brain, skeletal muscle, kidney and pancreas.
Description: The biological effects of IL-7 are mediated by the binding of IL-7 to the specific cell surface receptor complex. The functional high-affinity IL-7 receptor (IL-7 R) comprises the IL-7 R alpha chain in association with the common gamma chain (gamma c). Both IL-7 R alpha and gamma c are members of the hematopoietin receptor superfamily. Human and mouse IL-7 R alpha show 64% amino acid sequence identity. IL-7 R alpha transcripts were observed in murine spleen, thymus, fetal liver, developing T cells, B cells, mature T cells and bone marrow-derived macrophages.
Description: IL2-Ra is one of the three constituent subunits of the IL2 receptor. IL-2Ra is released into the serum after increased cellular expression such as increased activation of B and T cells. Clinical manifestations of IL2-Ra elevation include autoimmune conditions and some leukemias and lymphomas. Interleukin-2R Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain containing 192 amino acids (22-213) corresponding to the mature IL2-R protein with an amino terminal hexahistidine tag. The IL-2R is purified by proprietary chromatographic techniques.
Description: Interleukin 3 (IL-3) is a pleiotropic cytokine that can stimulate proliferation and differentiation of pluripotent hematopoietic stem cells as well as various lineage committed progenitors. IL-3 exerts its activity through binding to a specific cell surface receptor known as IL-3 R. IL-3 R is a heterodimeric structure composed of a 70 kDa IL-3 R alpha subunit (CD123 or beta common) and a 120-140 kDa IL-3 R beta subunit (CD131). CD131 also associates with the receptor for Erythropoietin, forming a tissue-protective hetero-receptor complex.
Description: The IL-2 receptor system consists of three non-covalently linked subunits termed IL-2R alpha, IL-2R beta, and IL-2R gamma. The IL-2R alpha is a type I transmembrane protein consisting of a 219 amino acid extracellular domain, a 19 amino acid transmembrane domain and a 13 amino acid intracellular domain, which is not involved in the transduction of IL-2 signals. Proteolytic processing of IL-2R alpha releases the entire extracellular domain of IL-2R alpha thereby generating a 219 amino acid soluble protein called soluble IL-2R alpha (sIL-2R alpha). The homodimeric form binds IL-2 (KD=10mM) and facilitates IL-2 signaling. The secreted sIL-2R alpha is expressed on leukemia cells, lymphoma cells, newly activated T and B cells, as well as on approximately 10% of NK cells. Recombinant human sIL-2R alpha is a 24.8 kDa protein containing 219 amino acid residues consisting of only the extracellular domain of IL-2R alpha. Due to glycosylation, IL-2R alpha has an approximate molecular weight of 31 kDa based on SDS-PAGE gel and Mass Spectrometry.
Description: Human and mouse IL-10 receptors are structurally related to the IFN-gamma receptor. These receptors are members of the class II subgroup of the cytokine receptor superfamily. The deduced amino acid sequence of human IL-10 R is approximately 60% identical to mouse IL-10 R. Although human IL-10 has cross-species activities and is active on mouse cells, mouse IL-10 is species-specific in its actions and does not bind to the human IL-10 receptor. The human IL-10 R gene has been mapped to chromosome 11q23.3. Recombinant IL-10 soluble receptor, consisting of the extracellular domain of IL-10 R, binds IL-10 with high affinity in solution and is a potent IL-10 antagonist.
Description: The biological activities of IL-12 are mediated through a receptor complex composed of two class I cytokine receptor subunits designated IL-12 R beta 1 and IL-12 R beta 2. Both subunits are required for high-affinity binding and activity of IL-12. IL-12 R beta 1 binds specifically to IL-12 p40, a subunit of the heterodimeric IL-12, and is also a subunit of the IL-23 receptor complex, while IL-12 R beta 2 binds IL-12 p35. IL-12 Rs are predominantly expressed on NK cells and activated T (Th1) cells with some expression also on dendritic cells. Both IL-12 R subunit extracellular domains are composed of three fibronectin-like domains and two cytokine receptor homology domains. IL-12R beta 2 also has an extracellular Ig-like domain.
Description: Two members of the type 5 subfamily of type I cytokine receptors can serve as receptors for IL-13. IL-13 can bind to IL-13 R alpha 1 (CD213a1; previously designated IL-13 R alpha or NR4) with low affinity, then recruits the IL-4 R alpha chain to form a high affinity receptor, causing downstream STAT6 activation. Alternately, IL-13 can bind IL-13 R alpha 2 (CD213a2) with high affinity; this interaction does not cause activation of STAT6, but does induce TGF-beta production. IL-13 R alpha 1 and IL-13 R alpha 2 each have three extracellular fibronectin type III domains, two cytokine receptor homology modules and a WSXWS motif typical of the class I cytokine receptor family, but IL-13 R alpha 2 has a much shorter cytoplasmic tail. IL-13 R subunits can be expressed on monocytes, macrophages, fibroblasts, human B cells, basophils, eosinophils, endothelial cells, and smooth muscle cells.
Description: Interleukin 15 receptor alpha (IL-15 R alpha) is a high affinity receptor that specifically binds IL-15 and associates as a heterotrimer with the IL-2 receptor beta and gamma subunits (Common gamma chain, or gamma c) to initiate signal transduction. IL-15 R alpha is expressed on a wide variety of Tand B cells as well as non-lymphoid cells. Human IL-15 R alpha shares 45% amino acid sequence homology with the mouse form of the receptor. Eight isoforms of IL-15 R alpha mRNA have been identified, resulting from alternative splicing events involving different exons.
Description: Human IL-18 R cDNA encodes a 541 amino acid (aa) precursor type I membrane protein with a hydrophobic signal, an extracellular domain comprised of three immunoglobulin-like domains, a transmembrane domain and a cytoplasmic region of approximately 200 aa residues. Human and mouse IL-18 R share 65% amino acid sequence homology. IL-18 R is widely expressed in numerous tissues including spleen, thymus, leukocyte, liver, lung, heart, small and large intestine, prostate and placenta
Description: IL-20 R alpha is widely expressed and is detected at high levels in multiple tissues including skin, testis, heart, placenta, salivary gland and prostate gland. The expression of IL-20 R alpha, together with that of IL-20 R beta, is upregulated in psoriatic skin lesions on keratinocytes, immune cells, and endothelial cells. IL-20 R alpha heterodimerizes with IL-20 R beta to form the functional receptor that mediates IL-19, IL-20 and IL-24 signals. IL-20 R alpha also heterodimerizes with IL-10 R beta to form the functional receptor complex for IL-26. Binding of these IL-10 family class II cytokines to their functional receptors induces activation of the JAK-STAT signal transduction pathway. At low ligand concentrations, STAT3 has been shown to be the predominant STAT proteins activated through either complexes.
Description: Human IL-2 exerts its biological effects via signaling through its receptor system, IL-2R. IL-2 and its receptor (IL-2R) are required for T-cell proliferation and other fundamental functions which are crucial of the immune response. IL-2R consists of 3 noncovalently linked type I transmembrane proteins which are the alpha (p55), beta (p75), and gamma (p65) chains. The IL-2R alpha chain contains an extracellular domain of 219 amino acids, a transmembrane domain of 19 amino acids, and an intracellular domain of 13 amino acids. The secreted extracellular domain of IL-2R alpha (s-IL-2R-a), also called TAC-antigen, is expressed on leukemia cells, lymphoma cells, approximately 10% NK cells, as well as recently activated T and B cells. Recombinant human s-IL-2R-a is a 24.8 kDa protein containing 219 amino acid residues consisting of only the extracellular domain of IL-2R alpha. Due to glycosylation, IL-2R alpha has an approximate molecular weight of 31 kDa based on SDS-PAGE gel and Mass Spectrometry.
Description: IL-1 receptor antagonist (IL-1ra) was originally isolated from the urine of patients with monocytic leukemia and has also been purified from adherent monocytes. The protein shows 26% amino acid homology to IL-1 beta and 19% homology to IL-1 alpha. It will compete with either factor for receptor binding, but does not interact with either one. Human IL-1ra will bind to both types of IL-1 receptor (I and II) on human cells. In mouse, IL-1RII does not bind IL-1ra.
Description: Quantitativesandwich ELISA kit for measuring Human Toll-like receptor 9, TLR-9 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Human Toll-like receptor 9, TLR-9 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
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Acute myeloid leukemia (AML) is one of the most serious blood cancers. Many studies have revealed that inflammation plays a vital role in the progression of hematopoietic malignants. Since the path of the till type 4 (TLR4), an important path involved in the induction of inflammation has already been associated with solid tumors, we hypothesized that it would be correlated with the physiopathological characteristics of patients AML and could be considered an anticancer target.
Parker
