Partners in crime: Autoantibodies complicit in COVID-19 pathogenesis.

Autoantibodies (AABs) play a critical role in the pathogenesis of autoimmune diseases (AIDs) and serve as a diagnostic and prognostic tool in assessing these complex disorders. Viral infections have long been recognized as a principal environmental factor affecting the production of AABs and the development of autoimmunity. COVID-19 has primarily been considered a hyperinflammatory syndrome triggered by a cytokine storm. In the following, the role of maladaptive B cell response and AABs became more apparent in COVID-19 pathogenesis. The current review will primarily focus on the role of extrafollicular B cell response, Toll-like receptor-7 (TLR-7) activation, and neutrophil extracellular traps (NETs) formation in the development of AABs following SARS-CoV-2 infection. In the following, this review will clarify how these AABs dysregulate immune response to SARS-CoV-2 by disrupting cytokine function and triggering neutrophil hyper-reactivity. Finally, the pathologic effects of these AABs will be further described in COVID-19 associate clinical manifestations, including venous and arterial thrombosis, a multisystem inflammatory syndrome in children (MIS-C), acute respiratory distress syndrome (ARDS), and recently described post-acute sequelae of COVID-19 (PASC) or long-COVID.

A novel water-soluble thiosemicarbazone Schiff base ligand and its complexes as potential anticancer agents and cellular fluorescence imaging.

A novel fluorescent ligand (H2LCl⋅1.5CH3OH, 1) was synthesized and metal complexes of 1 with Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) were obtained as Mn(HL)2Cl2 (2), Fe(HL)2Cl3⋅3H2O (3), Ni(L)(HL)Cl⋅8H2O (4), Cu(HL)Cl2⋅4H2O (5), Zn(H2L)Cl3 (6), respectively. These compounds were identified by spectroscopic methods, elemental analysis, molar conductivity, and single-crystal X-ray crystallography. According to the crystal structure of 4 nickel (II), center is surrounded by two ligands in a distorted octahedral geometry. The ligand and its complexes are soluble in water and have excellent stability. In vitro anti-proliferative activity of these compounds was evaluated against human breast adenocarcinoma (MCF-7) and human lipo-sarcoma (SW-872) as cancer cells and human fibroblasts (HFF-2) as normal cells by MTT assay. Interestingly, complex 5 exhibited excellent activity against both cancer cells with low IC50 value 22.18 ± 0.35 µg/mL (35.66 ± 0.56 µM) for SW-872 and 79.41 ± 3.54 µg/mL (127.6 ± 5.69 µM) for MCF-7 among the compounds and in comparison with paclitaxel (PTX) which acts finely. Morphological changes were evaluated by flow cytometry that revealed apoptosis is the main cause of cell death. Likewise, cell cycle studies indicated the cell cycle arrest in the G1 and S phases for complex 5 against MCF-7 and SW-872 cancer cells, while complex 6 could arrest the MCF-7 and SW-872 cells in G2 and G1 phases, respectively. All of the compounds are fluorescent which enabled us to monitor the uptake and intracellular distribution in living human cancer cells by fluorescence microscopy.

The evaluation of the MMP-2/TIMP-1 ratio in peptic ulcer and its association with refractory helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) is one of the leading causes of peptic ulcers, and its treatment is a worldwide challenge. Matrix metalloproteinases and their inhibitors influence the development and healing of peptic ulcers. This study aimed to evaluate the ratios of matrix metalloproteinase-2 (MMP-2) to tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with peptic ulcers that are sensitive or resistant to H. pylori treatment and compare them with healthy individuals. METHODS: In this study, 95 patients were included and divided into two groups sensitive (41 patients) and resistant to treatment (54 patients). The results were compared with a control group of 20 participants with normal endoscopy and H. pylori-negative. After obtaining written informed consent, five ml of venous blood was taken to determine their serum MMP-2 and TIMP-1 levels using an enzyme-linked immunosorbent assay. RESULTS: In patients with H. pylori-induced peptic ulcers, the MMP-2/TIMP-1 ratio was significantly higher than the healthy controls (P < 0.05). MMP-2 level was associated with patients' response to treatment (P < 0.05). The MMP-2/TIMP-1 ratio was higher in patients with simultaneous gastric and duodenal ulcers (P < 0.05). CONCLUSION: It seems that peptic ulcer disease caused by infection with H. pylori increases the MMP-2/TIMP-1 ratio in patients with peptic ulcers. However, it might not be a good predictor of refractory H. pylori-induced peptic ulcer disease.

Adverse Effects Reported and Insights Following Sinopharm COVID-19 Vaccination.

Vaccines are promising strategies for controlling COVID-19; however, COVID-19 vaccine side effects play a central role in public confidence in the vaccine and its uptake process. This study aimed to provide evidence on the post-vaccination early side effects of the BBIBP-CorV (Sinopharm) vaccine. This cross-sectional survey-based study was conducted between November 2021 and January 2022 among recipients of the BBIBP-CorV vaccine, using a questionnaire-based survey. Our final sample consisted of 657 participants, including 392 women. Among the study cases, only 103 (15.7%) participants received one dose of vaccine, and the rest received both doses (N = 554, 84.3%). Systemic symptoms (first dose: N = 187, both doses: N = 128) were the most commonly reported events after vaccination, and among them, injection site pain (first dose: 19.3%, both doses: 12.9%) was the most prevalent adverse effect. All reporting events were mild and resolved in less than 3 days without hospitalization. Among the participants, females and young people aged 35-65 were more prone to manifest side effects (N = 169, 53.3%) after the vaccine injection. Furthermore, our results revealed that the recipients who were suffering from underlying diseases, including diabetes, renal disorder, and respiratory illness, reported fewer adverse responses after vaccination in comparison with healthy individuals. Vaccination against SARS-CoV-2 may lead to some adverse reactions in recipients. However, the frequency of post-vaccination early side effects differed in people, but all responses were slight and temporary.

Association of carbapenem and multidrug resistance with the expression of efflux pump-encoding genes in Pseudomonas aeruginosa clinical isolates.

Efflux pumps play an important role in the emergence of antibiotic-resistant Pseudomonas aeruginosa strains. The present study aimed to assess the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps in carbapenem-resistant and multidrug-resistant (MDR) P. aeruginosa strains isolated from clinical specimens between June 2019 and January 2022 in Ardabil city. The presence of efflux pump-encoding genes, i.e. mexA, mexC, mexE, and mexY, was assessed using the polymerase chain reaction (PCR) technique in 48 carbapenem-resistant and MDR P. aeruginosa strains. Real-time reverse transcription PCR was employed to evaluate the expression levels of mexA, mexC, mexE, and mexY genes. All 48 carbapenem-resistant and MDR P. aeruginosa strains harbored efflux pump-encoding genes including mexA, mexC, mexE, and mexY according to the PCR results. Overexpression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps was detected in 75% (n = 36), 83.3% (n = 40), 10.4% (n = 5) and 41.6% (n = 20) of the clinical isolates of P. aeruginosa, respectively. This study revealed that the presence and overexpression of efflux pumps are associated with the emergence of carbapenem-resistant and MDR P. aeruginosa strains. Therefore, research on efflux pump inhibitors of P. aeruginosa will be a worthwhile endeavor to increase the clinical efficiency of available antibiotics and prevent ensuing treatment failure.

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19.

A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.

The tricks for fighting against cancer using CAR NK cells: A review.

Natural killer (NK) cells seem to be the most common innate lymphocyte subtypes, and they're known for their ability to guide anti-tumor and anti-viral responses, making them potentially therapeutic. Since NK cells lack polymorphic clonotypic receptors, they must rely on inhibitory receptors to develop, mature, and distinguish between "self" and "non-self." In the clinic, genetically engineered immune cells expressing a chimeric antigen receptor (CAR) that consists of an extracellular antigen recognizing domain connected to an intracellular signaling domain have gained interest. The U.S. food and drug administration (FDA) approved two CAR-T cells, anti-CD19 CARs, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). Nevertheless, CAR-T cell therapy is linked to a series of negative side effects, including fatal cytokine release syndrome (CRS) and tumor lysis syndrome (TLS), as well as a lack of regulatory control. CAR-transduced NK cells (CAR-NK) are thought to have many benefits, including clinical safety, the mechanisms by which they identify cancerous cells, and their abundance in clinical specimens, according to a growing number of studies. In pre-clinical and clinical trials, human primary NK cells and the NK-92 cell line were effectively transduced to express CARs against hematological cancers and solid tumors. Here, it is tried to summarize the development of CAR-NK cells, challenges and coping strategies, as well as managing the challenges and obstacles related to its protection, which promises to eliminate the shortcomings of conventional CARs.

MicroRNA-143 act as a tumor suppressor microRNA in human lung cancer cells by inhibiting cell proliferation, invasion, and migration.

BACKGROUND/AIM: MicroRNAs play crucial roles in controlling cellular biological processes. miR-143 expression is usually downregulated in different cancers. In this study, we focused on exploring the role of miR143 in NSCLC development. METHODS: Bioinformatics analyses were used to detect the expression level of miR-143 in lung tumors. The cells were transfected by pCMV-miR-143 vectors. The efficacy of transfection was verified by Flow cytometry. The influence of miR-143 replacement on NSCLC cells migration, proliferation, and apoptosis was detected using wound-healing assay, MTT assay, and DAPI staining, respectively. RESULTS: MTT assay revealed that overexpression of miR143 inhibited cell growth and proliferation. Scratch assay results demonstrated that restoration of miR143 suppressed cell migration. The qRT-PCR assay was further used to detect the assumed relationship between miR143 and apoptotic and metastatic-related genes. CONCLUSION: The findings showed that miR-143 could reduce cell proliferation, invasion, and migration by reducing CXCR4, Vimentin, MMP-1, Snail-1, C-myc expression level, and increasing E-cadherin expression levels in lung cancer cells and might be a potential target in NSCLC's targeted therapy.

Evaluation serum levels of Insulin Growth Factor-1 (IGF-1) and its association with clinical parameters in severe COVID-19.

BACKGROUND: Severe coronavirus disease-2019 (COVID-19) is associated with dysregulated immune response and extreme inflammatory injury. Considering the role of insulin growth factor-1 (IGF-1) in immune-mediated and inflammatory reactions, this study was conducted to investigate the IGF-1 contribution to the pathogenesis of severe form of COVID-19. MATERIAL AND METHODS: Sixty-two patients with severe COVID-19 and 52 healthy subjects were enrolled in this study. The serum levels of IGF-1 were measured using a solid-phase enzyme-linked chemiluminescent immunoassay on an Immulite 2000 system (Siemens Healthcare Diagnostics. RESULT: The serum levels of IGF-1 had no significant difference in COVID-19 patients compared to the healthy subjects (p = 0.359). There was a positive correlation between IGF-1 and age in the severe COVID-19 patients, while a negative correlation was observed for the serum levels of IGF-1 and age in the control group (r = 0.364, p = 0.036, r = - 0.536, p = 0.001, respectively). Moreover, IGF-1 was remarkably associated with hypertension, neurogenic disease, shock, and nausea in patients with the severe form of COVID-19 (p = 0.031, p = 0.044, p = 0.01, p = 0.03, respectively). CONCLUSION: Our results pointed to the complex role of IGF-1 in the severe form of COVID-19, and its association with clinical parameters, and some risk factors in the severe form of COVID-19.

Restoration of miR-330 expression suppresses lung cancer cell viability, proliferation, and migration.

Lung cancer is one of the most common cancers and its incidence is rising around the world. Various studies suggest that miR-330 acts as a tumor-suppressor microRNA (miRNA) in different types of cancers, but precisely how has remained unclear. In this study, we investigate miR-330 expression in lung cancer patient samples, as well as in vitro, by studying how normalization of miR-330 expression affects lung cancer cellular phenotypes such as viability, apoptosis, proliferation, and migration. We establish that low miR-330 expression predicts poor lung cancer prognosis. Stable restoration of reduced miR-330 expression in lung cancer cells reduces cell viability, increases the fraction of apoptotic cells, causes G2/M cell cycle arrest, and inhibits cell migration. These findings are substantiated by increased mRNA and protein expression of markers for apoptosis via the intrinsic pathway, such as caspase 9, and decreased mRNA and protein expression of markers for cell migration, such as vimentin, C-X-C chemokine receptor type 4, and matrix metalloproteinase 9. We showed that reduced miR-330 expression predicts poor lung cancer survival and that stable restoration of miR-330 expression in lung cancer cells has a broad range of tumor-suppressive effects. This indicates that miR-330 is a promising candidate for miRNA replacement therapy for lung cancer patients.

The sufficient vitamin D and albumin level have a protective effect on COVID-19 infection.

There is limited information regarding the protective factors of SARS-CoV-2 infection. This research is focused on analyzing the role of vitamin D and albumin in the severity, progression, or possible prevention of COVID-19 infection. In this case-control study, 191 patients and 203 healthy individuals were enrolled. Blood samples were taken to test the albumin and vitamin D levels of both groups. Our results show a direct association of vitamin D deficiency with the infection of COVID-19 and severity. According to our findings, 84.4% of patients with COVID-19 in this study had vitamin D deficiency. Moreover, the average level of albumin was significantly decreased in those infected patients who had respiratory symptoms. In the present study, a considerable negative correlation was established between the levels of vitamin D and the severity of COVID-19 infection. This reflects on the immunomodulatory and inhibitory nature of vitamin D to the viral replication.

The role of miR-34 in cancer drug resistance.

Resistance to conventional chemotherapy remains a major cause of cancer relapse and cancer-related deaths. Therefore, there is an urgent need to overcome resistance barriers. To improve cancer treatment approaches, it is critical to elucidate the basic mechanisms underlying drug resistance. Increasingly, the mechanisms involving micro-RNAs (miRNAs) are studied because miRNAs are also considered practical therapeutic options due to high degrees of specificity, efficacy, and accuracy, as well as their ability to target multiple genes at the same time. Years of research have firmly established miR-34 as a key tumor suppressor miRNA whose target genes are involved in drug resistance mechanisms. Indeed, numerous articles show that low levels of circulating miR-34 or tumor-specific miR-34 expression are associated with poor response to chemotherapy. In addition, elevation of inherently low miR-34 levels in resistant cancer cells effectively restores sensitivity to chemotherapeutic agents. Here, we review this literature, also highlighting some contradictory observations. In addition, we discuss the potential utility of miR-34 expression as a predictive biomarker for chemotherapeutic drug response. Although caution needs to be exercised, miR-34 is emerging as a biomarker that could improve cancer precision medicine.

siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468).

CD44, as a superficial cellular glycoprotein, is an essential factor in cell-cell and cell-matrix interaction. The CD44 expression level has been substantially up-regulated in breast cancer, and this upregulation facilitates tumor proliferation and angiogenesis. This study aims to evaluate the combination therapy of Jet Pei/CD44-specific-siRNA/doxorubicin in breast cancer MDA-MB468 cell line. The MTT assay, wound healing test, colony formation assay, DAPI staining, and flow cytometry were performed to investigate the tumoral cell viability, migration, clonogenesis, and apoptosis progression. The quantitative real-time PCR (qRT-PCR) was performed to demonstrate the CD44 expression level. Finally, the effect of CD44 silencing on the expression of VEGF, CXCR4, MMP9, and MiR-142-3p was measured. The combination of CD44-specific-siRNA with doxorubicin decreased tumoral metastasis, proliferation, invasion, and migration, and increased apoptosis in MDA-MB468 cells. In conclusions, CD44 can serve as a therapeutic target in breast cancer. Moreover, the combination therapy of CD44-specific-siRNA with doxorubicin can be a promising treatment for patients with breast cancer.

Targeting immune checkpoints: Building better therapeutic puzzle in pancreatic cancer combination therapy.

Pancreatic cancer is related to a very weak diagnosis; the close parallel between disease incidence and mortality rates from pancreatic cancer reflects the fatal nature of this disease. Although early detection procedures are growing, they are not applicable yet for pancreatic cancer. The majority of cancer patients suffer from advanced disease, in which surgery has no potential effect. Based on the growing evidence, it is predicated that cancer immunotherapy alone or in combination will probably be an essential section of different cancer treatment methods. There are different kinds of immune processes, including various antitumour and tumour-promoting leukocytes. Moreover, tumour cells utilise numerous approaches to overwhelm the immune response. Use of antibody in the therapeutic protocols is proving significant success and is probably a key element of cancer treatment. This method is directed against numerous negative immunologic regulators and immune checkpoints. In the present review, the clinical outlines of immune checkpoint inhibition are discussed in pancreatic cancer.

microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities.

Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. Features that distinguish them from the bulk of tumor cells include their pluripotency, self-renewal capacity, low proliferation rate, and tumor-initiating ability. CSCs are highly malignant, as they confer drug resistance and facilitate tumor progression, relapse, and metastasis. The molecular mechanisms underlying CSC biology are now beginning to be understood. In this context, microRNAs (miRNAs) occupy a prominent place. These endogenous, small noncoding RNA molecules control gene expression at the posttranscriptional level. This study reviews our current understanding of how the misexpression of tumor suppressor and oncogenic miRNAs in CSCs sustain their abundance and malignant properties. We discuss how they partly do so by acting on major CSC signaling pathways, including the Wnt, Notch, Hedgehog, and BMI-1 pathways. Our current knowledge of miRNA functions in CSCs may now be used for cancer diagnostic and prognostic purposes. In addition, when combined with recent technical advances in the in vivo delivery of miRNAs, we are now in an excellent position to develop strategies that harness miRNA interference and replacement technologies for the therapeutic targeting of CSCs.

Circulating myeloid-derived suppressor cells: An independent prognostic factor in patients with breast cancer.

Evading immune destruction is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3+ T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA-DR - CD33 + MDSCs in peripheral blood is about 10-fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA-DR - CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient-derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient-derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC.

Myeloid-derived suppressor cells: Important contributors to tumor progression and metastasis.

Myeloid-derived suppressor cells (MDSCs) are traditionally considered among the major components of the immunosuppressive tumor microenvironment (TME). However, there is currently increasing evidence indicating that MDSCs in addition to suppression of immune surveillance is also involved in an array of non-immunological functions like augmenting metastatic potential of tumor cells. Indeed, MDSCs can promote metastasis in animal models and cancer patients through promoting premetastatic niche formation, tumor angiogenesis and invasion. Moreover, MDSC frequency and function have been associated with progressive disease and correlated with clinical outcome. This review will summarize and discusses the data demonstrating the role for MDSCs in tumor metastasis.

The paradox of Th17 cell functions in tumor immunity.

Immune system acts as a host defensive mechanism protecting against attacking pathogens and transformed cells, including cancer cells. Th17 cells are a specific subset of T helper lymphocytes determined by high secretion of IL-17 and other inflammatory cytokines. Th17 cells increase tumor progression by activating angiogenesis and immunosuppressive activities. They can also mediate antitumor immune responses through recruiting immune cells into tumors, stimulating effector CD8+ T cells, or surprisingly by altering toward Th1 phenotype and producing IFN-γ, so Th17 cells are supposed as a double-edged sword in cancer. A comprehensive approach to indicating the activity of Th17 cells in tumor progression could help in the planning of new therapeutic approaches specially targeting Th17 cells in cancer.

Antiproliferative and apoptotic effects of a specific anti-insulin-like growth factor I receptor single chain antibody on breast cancer cells.

Insulin-like growth factor I receptor (IGF-IR) is expressed on breast cancer cells and involves in metastasis, survival, and proliferation. Currently, application of IGF-IR-targeting monoclonal antibodies (mAbs), alone or in combination with other drugs, is a promising strategy for breast cancer therapy. Single-chain fragment variable (scFv) antibodies have been introduced as appropriate tools for tumor-targeting purposes because of their advantages over whole antibodies. In the present study, we employed a naïve phage library and isolated scFvs against a specific epitope from extracellular domain of IGF-IR by panning process. The selected scFvs were further characterized using polyclonal and monoclonal phage ELISA, soluble monoclonal ELISA, and colony PCR and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies on breast cancer cell lines were also evaluated by MTT and Annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the IGF-IR peptide, and analyses of PCR product and sequencing confirmed the presence of full length VH and Vκ inserts. Treatment of MCF7 and SKBR3 cells with anti-IGF-IR scFv led to a significant growth inhibition. The results also showed that scFv treatment significantly augmented trastuzumab growth inhibitory effects on SKBR3 cells. The percentage of the apoptotic MCF7 and SKBR3 cells after 24-h treatment with scFv was 39 and 30.70 %, respectively. Twenty-four-hour treatment with scFv in combination with trastuzumab resulted in 44.75 % apoptosis of SKBR3 cells. Taken together, our results demonstrate that the targeting of IGF-IR by scFv can be an effective strategy in the treatment of breast cancer and provide further evidence for effectiveness of dual targeting of HER2 and IGF-IR in breast cancer therapy.

The role of adenosine and adenosine receptors in the immunopathogenesis of multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a heterogeneous neurological disorder with multifactorial etiologies characterized by demyelination, axonal degeneration, and oligodendroglial death. It is believed that both genetics and environmental risk factors such as infection are involved in disease etiology. Accumulating evidence indicates that alteration in purinergic system signaling is involved in immunity and inflammation. Adenosine, a key purine nucleoside, has been shown to be produced during metabolic stress, including ischemia, inflammatory condition, and tissue injury. METHODS: Extracellular adenosine directly affects various physiological and pathological processes of MS by stimulating G protein-coupled adenosine receptors A1, A2A, A2B, and A3 on the surface of immune cells. It has been suggested that promotion of adenosinergic system may be an important factor in MS pathophysiology and considered as promising therapeutic target for this disease. CONCLUSION: In this review, we will discuss about the immunopathologic effects of adenosine on MS and its animal model, experimental autoimmune encephalomyelitis.