Volume Articles

Increased mRNA expression of IL-23 in the peripheral blood of patients with multiple sclerosis

Ali Mehdizadeh¹, Vahid Shaygannejad^2*, Meysam Amidfar³, Seyed Javad Hasheminia⁴, Mohamad Mousaei Ghasroldasht⁵

¹School of medicine, Isfahan University of medical sciences, Isfahan, Iran.

²Isfahan neuroscience research center, alzahra research institute, Isfahan University of medical sciences, Isfahan, Iran.

³Tehran University of medical sciences, Tehran, Iran

⁴Department of immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

⁵Biology department, shahid ashrafi Isfahan University, clinical laboratory, alzahra hospital, Isfahan, Iran.

Background: interleukin-23 (IL-23) is a member of the IL-12 cytokine family that has shown through enhancement of T helper type 17 (Th17) cells expansion could play an important role in the inflammatory autoimmune responses in multiple sclerosis (MS).

Methods: The objective of the present study is to measure the relative expression of IL-23 mRNA in the peripheral blood of 15 MS patients in comparison with 15 healthy control subjects.

Results: the relative gene expression level of IL-23 in the peripheral blood cells from MS Patients was significantly increased compared to healthy controls (p < 0.001).

Conclusions: Our findings revealed upregulated gene expression pattern of IL-23 in the peripheral blood of MS patients that may be a peripheral marker for diagnosis of MS and might be a novel and promising therapeutic target for MS.

Mesenchymal stem cells: applications in immuno-cell therapy

Nasim Rahmani Kukia¹, Payam Zandi², Ardeshir Abbasi^3*

¹Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

²Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University Tehran, Iran

³Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Mesenchymal stromal cells(MSCs) have been exploited for their immunomodulatory properties in treating various immune-related disorders. MSCs can modulate the immune system through interactions with a variety of immune cells. Regardless of the researchers focused on understanding how MSCs connect to individual immune system cell subsets, the mechanisms for inducing restorative effect still stay mainly undiscovered. Through this mini-review we address what is known about the associations and effects of educated MSCs with cells of the innate immune system (macrophages and neutrophils) and our knowledge of these interactions will be essential in increasing and expanding new medical protocols for MSC based cell therapy in the foreseeable future.

Inflammatory Mechanisms Contributing to Aortic Expansion and Rupture after Acute Aortic Dissection

Atsushi Anzai*, Motoaki Sano

Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

In-hospital outcomes are generally acceptable with the conservative treatment of uncomplicated type B aortic dissection, but some patients present with undesirable complications, such as aortic expansion and rupture. Beyond mechanical and shear forces of blood flow affecting the weakened aortic wall, excessive inflammatory response has been shown to be associated with aortic expansion and adverse clinical outcomes. We have previously demonstrated the underlying mechanisms of catastrophic complications after acute aortic dissection (AAD) in mice. We propose that aortic dissection induces expression of the neutrophil chemoattractants CXCL1 and granulocyte-colony stimulating factor in the aortic tunica adventitia. These local environmental changes recruit neutrophils in combination with alteration of bone marrow milieu where reduced CXCL12 expression enhances neutrophil egress. Interleukin (IL)-6 production in the inflammatory adventitial neutrophils causes vascular inflammation, leading to vascular wall fragility. Targeting CXCR2 or IL-6 mitigates aortic expansion and prevents mice from aortic rupture. Collectively, adventitial neutrophil-mediated inflammation may be a potential therapeutic target to limit lethal complications after AAD.

Anti-inflammatory Approaches to Mitigate the Neuroinflammatory Response to Brain-Dwelling Intracortical Microelectrodes

Hillary W. Bedell^1,2 and Jeffrey R. Capadona^1,2*

¹Department of Biomedical Engineering, Case Western Reserve University, School of Engineering, 2071 MLK Jr. Drive, Wickenden Bldg, Cleveland OH 44106, USA

²Advanced Platform Technology Center, L. Stokes Cleveland VA Medical Center, Rehab. R&D, 10701 East Blvd. Mail Stop 151 AW/APT, Cleveland OH 44106, USA

Intracortical microelectrodes are used both in basic research to increase our understanding of the nervous system and for rehabilitation purposes through brain-computer interfaces. Yet, challenges exist preventing the widespread clinical use of this technology. A prime challenge is with the neuroinflammatory response to intracortical microelectrodes. This mini-review details immunomodulatory strategies employed to decrease the inflammatory response to these devices. Over time, broad-spectrum anti-inflammatory approaches, such as dexamethasone and minocycline, evolved into more targeted treatments since the underlying biology of the neuroinflammation was elucidated. This review also presents studies which examine novel prospective targets for future immunomodulatory targeting.

T Cells in Atherosclerosis in Ldlr-/- and Apoe-/- Mice

Godfrey S. Getz^1* and Catherine A. Reardon²

¹Department of Pathology, The University of Chicago, Chicago, IL 60637, USA

²Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL 60637, USA

Atherosclerosis is the underlying basis for most cardiovascular diseases. It is a chronic inflammation affecting the arterial intima and is promoted by hypercholesterolemia. Cells of both the innate and adaptive immune systems contribute to this inflammation with macrophages and T cells being the most abundant immune cells in the atherosclerotic plaques. In this review, we discuss the studies that examined the role of T cells and T cell subsets in Apoe-/- and Ldlr-/- murine models of atherosclerosis. While there is a general consensus that Th1 cells are pro-atherogenic and regulatory T cells are atheroprotective, the role of other subsets is more ambiguous. In addition, the results in the two models of atherosclerosis do not always yield similar results. Additional studies in the two murine models using cell specific gene manipulations are needed.

Identification of ω-sites of Glycosylphosphatidylinositol Anchored Proteins

Yusuke Masuishi*, Shota Endo, Hideaki Kasuga, Tomoo Hidaka, Takeyasu Kakamu, Tetsuhito Fukushima

Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, 1Hikariga-oka, Fukushima City 960-1295, Japan

Unique and complex post-translational modifications are present in the outer leaflet of the plasma membrane. Glycosylphosphatidylinositol (GPI) anchoring is essential for the expression of several outer membrane proteins on the cell surface. A common GPI anchor structure is constituted by glycan moiety, lipid moiety, phosphate and ethanolamine. GPI-anchored proteins (GPI-APs) are observed among eukaryotic species. Abnormal GPI anchoring of proteins is thought to cause various diseases such as paroxysmal nocturnal hemoglobinuria. Recently, many inherited GPI deficiencies (IGDs) have been reported to cause epilepsy, mental retardation, coarse facial features, and multiple organ anomalies. Diseases caused by abnormal GPI anchoring will probably continue to increase, because it is still unknown how many causative genes of IGDs are present. Therefore, in order to study these diseases, the analytical methods of GPI-APs will become important in the future. To date, many methods have been developed for analysis of GPI- APs. In this review, we attempt to summarize the present knowledge about comprehensive analytical methods of GPI-APs and introduce briefly some GPI anchor-related diseases.

A Flow Cytometric Immunophenotyping Approach to the Detection of Regulated Cell Death Processes

A Vossenkamper¹, G Warnes^2*

¹Centre for Immunobiology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary London University, 4 Newark Street, London E1 2AT, UK

²Flow Cytometry Core Facility, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary London University, 4 Newark Street, London E1 2AT, UK

The use of the Western Blot technique has been the gold standard to determine protein expression and to semi-quantitate this expression in cell lysates. The recent publication of a flow cytometric immunophenotyping method employing fluorescently labelled antibodies to the intracellular labelling of antigens involved in Regulated Cell Death (RCD) processes has allowed the detection of three of these processes simultaneously which gave clarity to the interpretation of the relationship between apoptosis, RIP1 dependent apoptosis and necroptosis. Flow cytometry can now immunophenotype necroptosis by virtue of the up-regulation of RIP3 with simultaneous estimations of the degree of classic apoptosis (Caspase-3^+ve/RIP3^-ve) and of RIP1-dependent apoptosis (Caspase-3^+ve/RIP3^+ve) in live and dead cell populations. This approach for detecting multiple forms of cell death has been confirmed by the use of apoptosis and necroptosis blocking agents, zVAD and necrostatin-1 after treatment with etoposide or shikonin which induced apoptosis and necroptosis. The addition of anti-PARP and H2AX antibodies for the detection of parthanatos and DNA damage showed that double negative Caspase-3^-ve/RIP3^-ve cells detected in a previous study have undergone parthanatos or still display a negative phenotype for any cell death process.

Pathological Approach to A Special Benign Tumor with Regard to its Differential Diagnose Spectrum: Intranodal Palisaded Myofibroblastoma

Yasemin Yuyucu Karabulut*

Mersin University Medical School, Department of Pathology, Mersin, Turkey

Intranodal palisaded myofibroblastoma, also known as “intranodal hemorrhagic spindle cell tumor with amianthoid fibers,” is a benign mesenchymal tumor of the lymph node originating from smooth muscle cells and myofibroblasts often with the presence of amianthoid fibers. Ninety-three cases of intranodal palisaded myofibroblastoma have been reported in the literatüre since its first description and most of them have the same clinical history “painless firm nodüle”. It is mostly seen in inguinal region there are few cases have been described in other locations. It’s large and important differential diagnostic spectrum makes this tumor special.

Demonstration of Mosquito Midgut Antigen for the Effective Control of Mosquito Population

Sabahat Abdullah, Sajjad Ur Rahman, Ahsan Naveed*, Qamar Majeed

Institute of Microbiology, University of Agriculture Faisalabad, 3840, Pakistan

Mosquito-borne diseases can be reduced drastically with the aid of vaccines which provoke mosquitocidal or mosquito-killing effect. The midgut of mosquito performs a fundamental role in the development and the transmission of ailment. Anti-midgut antibodies show the extensive variety of activity, blockading the development of pathogen in various species of mosquitoes. In addition to reducing the egg-laying ability of mosquitoes and survivorship also block the transmission activity of pathogen. Mitsuhashi and Maramorosch media was used to culture the mosquito midgut cells. The cells were formalin inactivated and injected into the rabbits in plain and adjuvanted form to raise hyperimmune serum. The serum was processed for IHA and serum showing high titre were selected for blood feeding assay. The blood from the rabbits was fed to the mosquitos to observe the mosquitocidal effect of the antigen. In blood feeding assay killing of mosquitoes was also observed after regular interval of time. The overall results proved that mosquito midgut contains antigenic peptides that may be able to induce the antibody response. These antigenic peptides somehow irritate digestive mucosa of the mosquitoes on blood feeding and have the potential to kill or reduce the mosquito population.