Role of PD-1 in Immunity and Diseases
EMERGING CONCEPTS TARGETING IMMUNE CHECKPOINTS IN CANCER AND AUTOIMMUNITY
Authors: Chamoto, Kenji; Al-Habsi, Muna; Honjo, Tasuku
Abstract
Immunity developed to defend our bodies from foreign particles, including bacteria and viruses. Although effector cells responsible for acquired immunity, mainly T cells, and B cells, are able to distinguish self from non-self, they sometimes attack the body's tissues because of imperfect central tolerance. Several immune check points developed to limit overactivation of these cells. One of the most important immune checkpoints is programmed cell death-1 (PD-1), which is expressed mainly on activated lymphocytes. As its ligands (PD-Ls) are expressed widely in the body and affect the responses against self and foreign antigens, controlling PD-1/PD-L interactions enables the management of several immune-related diseases such as autoimmune disease, virus infection, and cancers. Currently, the strategy of PD-1/PD-L1 blockade has already been applied to clinical cancer therapy, providing evidences that PD-1 signal is one of the main factors of cancer immune escape in humans. The dramatic efficacy of PD-1 blockade in cancer immunotherapy, promises the control of other immune diseases by PD-1 signal modulation. In this review, we summarize the history of PD-1, subsequent basic studies, and their application to the clinic.
Nanocurcumin is a potential novel therapy for multiple sclerosis by influencing inflammatory mediators
PHARMACOLOGICAL REPORTS
Authors: Dolati, Sanam; Ahmadi, Majid; Aghebti-Maleki, Leili; Nikmaram, Abbas; Marofi, Faroogh; Rikhtegar, Reza; Ayromlou, Hormoz; Yousefi, Mehdi
Abstract
Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Inflammation has ever been thought as disadvantageous in the pathophysiology of MS. Nanocurcumin has been used as an anti-inflammatory compound. The aim of this study was to identify effects of nanocurcumin on inflammatory mediators in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Fifty MS patients were randomly divided into two groups. The test group received nanocurcumin capsule daily for 6 months. Simultaneously, the control group received placebo. Real-Time PCR was employed to detect the probable changes in gene expression levels of miRNAs, and miRNA-dependent targets, and also transcription factors and pro-inflammatory cytokines in blood samples. ELISA was used to determine the alterations in these cytokines secretion levels. We have also examined EDSS score in MS patients in two groups. Results: According to the results, a significant decrease in mRNA expression levels of miR-145 (p < 0.0001), miR-132 (p = 0.004), miR-16 (p = 0.0034), STAT1 (p = 0.0002), NF-kappa B (p < 0.0001), AP-1 (p = 0.0007), IL-1 beta (p = 0.0017), IL-6 (p = 0.017), IFN-gamma (p < 0.0001), CCL2 (p = 0.0067), CCL5 (p = 0.0034), TNF-alpha (p < 0.0001) and also significant increase in expression levels of miRNAs targets; Sox2 (p = 0.0001), sirtuin-1(p = 0.0007), Foxp3 (p = 0.0082), PDCD1 (p = 0.003) was evident in nanocurcumin treated group compared with before treatment. The secretion levels of IFN-gamma (p = 0.0025), CCL2 (p = 0.0029), and CCL5 (p = 0.0003) were reduced dramatically in test group compared with placebo group. Conclusion: In conclusion, nanocurcumin may be more effective on the inflammatory features of MS. According to present results, nanocurcumin may inhibit neuroinflammation in MS patients. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.