The effect of lipopolysaccharide on the expression level of immunomodulatory and immunostimulatory factors of human amniotic epithelial cells

Objective Human amniotic epithelial cells (hAECs) are a novel source of stem cells and have immunomodulatory effects on both the innate and adoptive immune system. hAECs can differentiate into multiple cell lineages that make them a suitable cell source for regenerative medicine. These cells express multiple toll-like receptors (TLRs) and respond to various TLR ligands. This study aimed to evaluate the effect of lipopolysaccharide (LPS), a TLR4 ligand, on the level of immunomodulatory and immunostimulatory factors of hAECs. Results Our results indicated that LPS had the ability to up-regulate the expression of prostaglandin E2 synthase and transforming growth factor-beta1 in hAECs. However, there was no change in the level of interleukin-1beta, interleukin-6 and interleukin-10 in hAECs when were stimulated with LPS. In addition, we observed tumor necrosis factor-alpha was only expressed at very low level in some of hAECs samples which its expression was independent of the effects of LPS. Keywords: Human amniotic epithelial cells Toll-like receptors Lipopolysaccharide Immunomodulatory effects Regenerative medicin

Vaccine potential of lena and lcpa proteins of leptospira interrogans in combination with escherichia coli heat-labile enterotoxin, b subunit (LTB)

Background and Objectives: Leptospirosis is a zooanthroponosis caused by the genus of Leptospira. It is an emerging public health problem due to its increasing incidence. The achievement to a vaccine that prevent from entrance of Leptospira interrogans to the deeper tissues of the host is needed. This study aimed to investigate the immunogenicity of LcpA (rLcpA) and LenA (rLenA) recombinant proteins in combination with LTB (rLTB) recombinant protein as an adjuvant against leptospiral infection in hamsters. Materials and Methods: The genes encoding these proteins were cloned into pGH cloning vector and then lenA, lcpA and ltb genes subcloned into pET-15b and pET-28a expression vectors, respectively. The hamsters were immunized with the purified recombinant proteins and challenged with Leptospira interrogans for evaluation of their survival. The antibody responses to the recombinant proteins were determined by ELISA. Then, data entered into SPSS software. Statistical Kruskal-Wallis test was used to compare the significant differences among different groups. The groups with significant differences were further analyzed by post hoc tests. The p value < 0.05 statistically was considered significant. Results: Immunized hamsters with rLenA-plus-rLTB, rLcpA-plus-rLTB and rLenA-plus-rLcpA-plus-rLTB proteins showed 60, 74, and 80 survival rates, respectively. A significant amount of interleukin-17 (IL-17), interleukin-4 (IL-4) and gamma interferon (IFNγ) cytokines were produced in immunized hamsters. Conclusion: Based on our findings, rLcpA and rLenA proteins in combination with rLTB can protect the hamsters against L. interrogans and effectively induce a protective antibody response. Thus, these proteins can be used as an additional prophylactic tool against leptospira. © 2018, Tehran University of Medical Science. All rights reserved

Albumin and multiple sclerosis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Leakage of the blood–brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth

The effect of Isosorbide Dinitrate on vascular endothelial growth factor production by human leukemic cell lines in vitro

&quot;nBackground: Vascular endothelial growth factor (VEGF) has mitogenic effect for endothelial cells and is an important mediator of tumor expansion, metastasis and angiogenesis in vivo. Isosorbide dinitrate, as a nitric oxide donor, has been widely used in treatment of many cardiovascular diseases such as congestive heart failure and acute coronary syndromes. Furthermore this drug was found to have inhibitory effect on angiogenesis, tumor growth and metastasis in vivo. In the present study we evaluated the isosorbide effect on the VEGF production using some human leukemic cell lines. &quot;nMethods: Human leukemic MOLT-4, JURKAT and U937 cells were cultured in complete RPMI medium. The cells at the exponential growth phase were then incubated with different concentrations of Isosorbide (4&amp;acute;10-7 -4&amp;acute;10-4 M) in the presence or absence of PMA (25ng/ml) for 24 hours. The VEGF concentrations in the culture supernatants were measured by enzyme immunoassay kits (R&amp;amp;D systems) according to the manufacturer&apos;s instructions. &quot;nResults: The level of VEGF produced by the human leukemic cell lines which was treated with different concentrations of isosorbide, did not show any significant difference with untreated control cells. &quot;nConclusions: The results of this study showed that isosorbide had no significant effect on VEGF production. Our findings suggest that anti-angiogenesis effect of isosorbide could be mediated through VEGF-independent mechanism(s). Further studies are warranted to determine definite isosorbide effect on VEGF and other angiogenic factors production in patients as well as animal models

Opioids and opioid receptors in multiple sclerosis

Central neuropathic pain is common in multiple sclerosis (MS) initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in about 28 of patients with multiple sclerosis. The mechanistic basis for this increased nociception is currently poorly understood. The opioids provide excellent pain relief in most patients. While neuropathic pain in MS is poorly responsive but not totally unresponsive to opioids. The results do not support the routine use of strong opioids in MS patients with central pain. The possible link between the opioid peptides and the heterogeneity of the clinical course of multiple sclerosis was investigated. Based on the researches that have been carried out, they become apparent that ongoing learning about receptor subtypes and related opioid analgesics must take place to understand the complexity of pain management. In this article, our aim is to investigate the mechanism of effect opioid and opioid receptor and describe previous experiments as application cases of opioids and opiates for pain relief in MS patients

Effects of &beta;-D-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, ROR&gamma;t, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

Anis Barati,1 Ahmad Reza Jamshidi,2,* Hossein Ahmadi,1 Zahra Aghazadeh,1 Abbas Mirshafiey1,* 1Department of Immunology, School of Public Health, 2Iranian Institute for Health Sciences Research, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of &beta;-D-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, ROR&gamma;t, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500&nbsp;mg twice daily for 12&nbsp;weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and ROR&gamma;t. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and ROR&gamma;t levels but also increase IL4 and GATA3 levels after 12&nbsp;weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2). Keywords: M2000, IL17, ROR&gamma;t, rheumatoid arthritis, inflammation, immunosuppressiv