BackgroundInflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology.ObjectiveWe sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.MethodsMice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.ResultsMice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release.ConclusionsMitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation. Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD.
The lymph node follicular dendritic cell (FDC) network is derived from the expansion and differentiation of marginal reticular cells, as are the new FDCs generated during an immune response.
Nonhematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures, such as lymph node (LN) trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. IL-7 is an important stromal cell-derived cytokine that has been considered to be derived mainly from T-cell zone fibroblastic reticular cells. We show here that lymphatic endothelial cells ( IntroductionIL-7 is an important cytokine that controls development and activation of different immune cells. 1 The broad expression of this cytokine in primary and secondary lymphoid organs is indicative for its multiple functions. In bone marrow, IL-7 acts on the development of B cells by determining B-cell lineage commitment 2 and regulating immunoglobulin gene arrangement. 3,4 In the thymus, IL-7 serves as a key factor for thymocyte survival and maturation. 5,6 Likewise, IL-7 provides antiapoptotic and proliferative signals to T cells within secondary lymphoid organs and is hence critical for peripheral T-cell homeostasis. 7,8 Furthermore, some intrinsic functions of marginal zone B cells and structural organization of the splenic marginal zone microenvironment depend, at least partially, on IL-7. 9 Besides these effects on T and B lymphocytes, IL-7 can impact on the development of dendritic cells 10 and NK T cells. 11 Hence, because of its pleiotropic functions, IL-7 can be regarded as one of the central regulators of immune cell homeostasis.Besides its direct impact on immune cells, IL-7 acts also on the formation of secondary lymphoid organs. During lymph node (LN) development, for example, IL-7 is produced by VCAM1 ϩ ICAM1 ϩ mesenchymal cells, also known as stromal organizer cells. 12 Stromal cell-derived IL-7 promotes survival of lymphoid tissue inducer (LTi) cells 13 that initiate lymphotoxin- receptor-dependent formation of the LN environment. 14 The importance of IL-7 in LN development and maturation is illustrated by the absence of most peripheral LNs in IL-7R␣-deficient mice. 15,16 Furthermore, overexpression of IL-7 results in the formation of ectopic lymphoid tissues, 17 suggesting that IL-7 critically contributes to the adaptation of lymphoid organ structure during immune reactions.IL-7 production is tightly regulated and detection of both IL-7 protein and mRNA in situ requires highly sensitive detection systems. 18 It has been suggested that IL-7 produced by stromal cells in secondary lymphoid organs is locally consumed by IL-7R␣-expressing cells and that a production-consumption equilibrium regulates lymphocyte homeostasis. 19 Indeed, a recent study suggested that T-cell homeostasis is controlled by T-cell zone fibroblastic reticular cells (FRCs), which exhibited higher IL-7 expression compared with bulk endothelial cell preparations. 20 However, not all IL-7R␣-expressing cells reside in the T-cell zone. For example, IL-7R␣ ϩ ␥␦ T cells ...
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.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.