Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MS(n) ). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4(+) and activated CD4(+) CD25(+) T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.
Nuclear protein 1 (NUPR1) is a transcription cofactor that senses stressful conditions and modulates cellular response by promoting or inhibiting apoptosis. NUPR1 is usually highly expressed in tumor cells where it enables them to adapt and resist environmental stress or chemotherapeutic compounds. NUPR1 can be involved in cell proliferation. Data about the involvement of NUPR1 in the proliferation and apoptosis of lymphocytes are scarce. Therefore, in this study we focused on the role of NUPR1 in lymphocyte physiology and found that NUPR1 might be involved in the initiation of their proliferation. Lymphocytes were isolated from the cervical lymph nodes of C57BL/6 mice. NUPR1 expression subsided 24 h after the induction of proliferation by a mitogen. Also, stressful conditions after cell isolation led to increased NUPR1 mRNA and protein expression in vitro that coincided with cell apoptosis. Similarly, apoptosis induction by staurosporine, a broadrange protein kinase inhibitor, led to increased NUPR1 expression. In addition, NUPR1 inhibition by small-interfering RNA prevented the staurosporine-induced apoptosis (judging from decreased caspase activity) in the whole cell population of cervical lymph nodes. However, NUPR1 absence was irrelevant to the induction of apoptosis in CD3 + T lymphocytes, suggesting that NUPR1 is probably a mediator of apoptosis in other immune cell populations within the lymph node, such as B lymphocytes. In conclusion, our results suggest that NUPR1 is important for the initiation of lymphocyte cell division and for the apoptotic process of non-T cells during stressful conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.