Guzman-Beltran S.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas
Oxidative Medicine and Cellular Longevity | Year: 2013
Curcumin is a bifunctional antioxidant derived from Curcuma longa. This study identifies curcumin as a neuroprotectant against hemin-induced damage in primary cultures of cerebellar granule neurons (CGNs) of rats. Hemin, the oxidized form of heme, is a highly reactive compound that induces cellular injury. Pretreatment of CGNs with 5-30 M curcumin effectively increased by 2.3-4.9 fold heme oxygenase-1 (HO-1) expression and by 5.6-14.3-fold glutathione (GSH) levels. Moreover, 15 M curcumin attenuated by 55% the increase in reactive oxygen species (ROS) production, by 94% the reduction of GSH/glutathione disulfide (GSSG) ratio, and by 49% the cell death induced by hemin. The inhibition of heme oxygenase system or GSH synthesis with tin mesoporphyrin and buthionine sulfoximine, respectively, suppressed the protective effect of curcumin against hemin-induced toxicity. These data strongly suggest that HO-1 and GSH play a major role in the protective effect of curcumin. Furthermore, it was found that 24 h of incubation with curcumin increases by 1.4-, 2.3-, and 5.2-fold the activity of glutathione reductase, glutathione S-transferase and superoxide dismutase, respectively. Additionally, it was found that curcumin was capable of inducing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus. These data suggest that the pretreatment with curcumin induces Nrf2 and an antioxidant response that may play an important role in the protective effect of this antioxidant against hemin-induced neuronal death. © 2013 Susana González-Reyes et al.
Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas, University of Chicago and University of Pittsburgh | Date: 2014-05-14
The present invention relates to the discovery that of a panel of serum or plasma markers may be used to diagnose Idiopathic Pulmonary Fibrosis (IPF) and distinguish this condition from other lung ailments. It further relates to the identification of markers associated with IPF disease progression.
Pardo A.,National Autonomous University of Mexico |
Pardo A.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Selman M.,National Autonomous University of Mexico |
Selman M.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas
Fibrogenesis and Tissue Repair | Year: 2012
Lung fibrosis is the final common pathway of a large variety of chronic lung disorders, named interstitial lung diseases. The most aggressive form is the idiopathic pulmonary fibrosis [IPF] characterized by alveolar epithelial cell injury/activation, expansion of the fibroblast/myofibroblast population, and the exaggerated accumulation of extracellular matrix [ECM] components which ultimately result in the destruction of the lung parenchyma. Several matrix metalloproteases [MMPs] are upregulated in the IPF lungs and have been shown to actively participate in the pathogenesis of the disease through extracellular matrix remodeling and basement membrane disruption. However, MMPs can also breakdown molecules that mediate cell-cell and cell-ECM interactions, and can activate growth factors and growth factor receptors indicating that they likely contribute to other local biopathological processes such as apoptosis, migration, proliferation and angiogenesis. © 2012 Pardo and Selman; licensee BioMed Central Ltd.
Garcia-de-Alba C.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Becerril C.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Ruiz V.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Gonzalez Y.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
And 4 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010
Rationale: Fibrocytes are progenitor cells characterized by the simultaneous expression of mesenchymal, monocyte, and hematopoietic stem cell markers. We previously documented their presence in lungs of patients with idiopathic pulmonary fibrosis. However, the mechanisms involved in their migration, subsequent homing, and local role remain unclear. Matrix metalloproteinases (MMPs) facilitate cell migration and have been implicated in the pathogenesis of pulmonary fibrosis. Objectives: To evaluate the expression and role of matrix metalloproteinases in human fibrocytes. Methods: Fibrocytes were purified from CD14+ monocytes and cultured for 8 days; purity of fibrocyte cultures was 95% or greater as determined by flow cytometry. Conditioned media and total RNA were collected and the expression of MMP-1, MMP-2, MMP-7, MMP-8, and MMP-9 was evaluated by real-time polymerase chain reaction. Protein synthesis was examined using a Multiplex assay, Western blot, fluorescent immunocytochemistry, and confocal microscopy. MMP-2 and MMP-9 enzymatic activities were evaluated by gelatin zymography. Migration was assessed using collagen I-coated Boyden chambers. Stromal cell-derived factor-1α and platelet-derived growth factor-B were used as chemoattractant with or without a specific MMP-8 inhibitor. Measurements and Main Results: Fibrocytes showed gene and protein expression of MMP-2, MMP-9, MMP-8, and MMP-7. MMP-2 and MMP-9 enzymatic activities were also demonstrated by gelatin zymography. Likewise, we found colocalization of MMP-8 and MMP-7 with type I collagen in fibrocytes. Fibrocyte migration toward platelet-derived growth factor-B or Stromal cell-derived factor-1α in collagen I-coated Boyden chambers was significantly reduced by a specific MMP-8 inhibitor. Conclusions: Our findings reveal that fibrocytes express a variety of MMPs and that MMP-8 actively participates in the process of fibrocyte migration.
Selman M.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Pardo A.,National Autonomous University of Mexico
American Journal of Respiratory and Critical Care Medicine | Year: 2014
A growing body of evidence indicates that aberrant activation of alveolar epithelial cells and fibroblasts in an aging lung plays a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the biopathological processes linking aging with IPF and the mechanisms responsible for the abnormal activation of epithelial cells and fibroblasts have not been elucidated. Many of the hallmarks of aging (e.g., genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, and cellular senescence) have been proposed as essential mechanisms for the development of IPF; however, these disturbances are not restricted to IPF and also occur in other aging-related lung disorders, primarily chronic obstructive pulmonary disease (COPD). Therefore, an unanswered question is why a current/former smoker of about 60 years of age with shorter telomeres, alveolar epithelial senescence, excessive oxidative stress, and mitochondrial dysfunction develops IPF and not COPD; in other words, what makes old lungs specifically susceptible to develop IPF? In this Perspective, we propose an integral model in which the combination of some gene variants and/or gene expression in the aging lung results in the loss of epithelial integrity and consequently in the failure of the alveoli to correctly respond to injury and to face the stress associated with mechanical stretch. Afterward, a distinctive epigenetic "reprogramming" that affects both epithelial cells and fibroblasts provokes, among others, the recapitulation of developmental pathways and the aberrant activation and miscommunication between both cell types, resulting in the exaggerated production and accumulation of extracellular matrix and the subsequent destruction of the lung architecture. Copyright © 2014 by the American Thoracic Society.
Guzman-Beltran S.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Perez-Torres A.,National Autonomous University of Mexico |
Coronel-Cruz C.,National Autonomous University of Mexico |
Torres-Guerrero H.,National Autonomous University of Mexico
Microbes and Infection | Year: 2012
Sporothrix schenckii is a human pathogen that causes sporotrichosis, a cutaneous subacute or chronic mycosis. Little is known about the innate immune response and the receptors involved in host recognition and phagocytosis of S. schenckii. Here, we demonstrate that optimal phagocytosis of conidia and yeast is dependent on preimmune human serum opsonisation. THP-1 macrophages efficiently ingested opsonised conidia. Competition with d-mannose, methyl α- d-mannopyranoside, d-fucose, and N-acetyl glucosamine blocked this process, suggesting the involvement of the mannose receptor in binding and phagocytosis of opsonised conidia. Release of TNF-α was not stimulated by opsonised or non-opsonised conidia, although reactive oxygen species (ROS) were produced, resulting in the killing of conidia by THP-1 macrophages. Heat inactivation of the serum did not affect conidia internalization, which was markedly decreased for yeast cells, suggesting the role of complement components in yeast uptake. Conversely, release of TNF-α and production of ROS were induced by opsonised and non-opsonised yeast. These data demonstrate that THP-1 macrophages respond to opsonised conidia and yeast through different phagocytic receptors, inducing a differential cellular response. Conidia induces a poor pro-inflammatory response and lower rate of ROS-induced cell death, thereby enhancing the pathogen's survival. © 2012 Institut Pasteur.
Zuniga J.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas
Clinical & developmental immunology | Year: 2012
Mycobacterium tuberculosis (Mtb) infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs). We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB.
Prado-Garcia H.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Romero-Garcia S.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Aguilar-Cazares D.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Meneses-Flores M.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Lopez-Gonzalez J.S.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas
Clinical and Developmental Immunology | Year: 2012
Lung cancer is the leading cause of cancer deaths worldwide and one of the most common types of cancers. The limited success of chemotherapy and radiotherapy regimes have highlighted the need to develop new therapies like antitumor immunotherapy. CD8+ T-cells represent a major arm of the cell-mediated anti-tumor response and a promising target for developing T-cell-based immunotherapies against lung cancer. Lung tumors, however, have been considered to possess poor immunogenicity; even so, lung tumor-specific CD8+ T-cell clones can be established that possess cytotoxicity against autologous tumor cells. This paper will focus on the alterations induced in CD8+ T-cells by lung cancer. Although memory CD8+ T-cells infiltrate lung tumors, in both tumor-infiltrating lymphocytes (TILs) and malignant pleural effusions, these cells are dysfunctional and the effector subset is reduced. We propose that chronic presence of lung tumors induces dysfunctions in CD8+ T-cells and sensitizes them to activation-induced cell death, which may be associated with the poor clinical responses observed in immunotherapeutic trials. Getting a deeper knowledge of the evasion mechanisms lung cancer induce in CD8+ T-cells should lead to further understanding of lung cancer biology, overcome tumor evasion mechanisms, and design improved immunotherapeutic treatments for lung cancer. © 2012 Heriberto Prado-Garcia et al.
Munoz-Hernandez B.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Palma-Cortes G.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Cabello-Gutierrez C.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas |
Martinez-Rivera M.A.,National Polytechnic Institute of Mexico
BMC Infectious Diseases | Year: 2014
Background:Coccidioides spp. is the ethiological agent of coccidioidomycosis, an infection that can be fatal. Its diagnosis is complicated, due to that it shares clinical and histopathological characteristics with other pulmonary mycoses. Coccidioides spp. is a dimorphic fungus and, in its saprobic phase, grows as a mycelium, forming a large amount of arthroconidia. In susceptible persons, arthroconidia induce dimorphic changes into spherules/endospores, a typical parasitic form of Coccidioides spp. In addition, the diversity of mycelial parasitic forms has been observed in clinical specimens; they are scarcely known and produce errors in diagnosis. Methods: We presented a retrospective study of images from specimens of smears with 15% potassium hydroxide, cytology, and tissue biopsies of a histopathologic collection from patients with coccidioidomycosis seen at a tertiary-care hospital in Mexico City. Results: The parasitic polymorphism of Coccidioides spp. observed in the clinical specimens was as follows: i) spherules/endospores in different maturation stages; ii) pleomorphic cells (septate hyphae, hyphae composed of ovoid and spherical cells, and arthroconidia), and iii) fungal ball formation (mycelia with septate hyphae and arthroconidia).Conclusions: The parasitic polymorphism of Coccidioides spp. includes the following: spherules/endospores, arthroconidia, and different forms of mycelia. This knowledge is important for the accurate diagnosis of coccidioidomycosis. In earlier studies, we proposed the integration of this diversity of forms in the Coccidioides spp. parasitic cycle. The microhabitat surrounding the fungus into the host would favor the parasitic polymorphism of this fungus, and this environment may assist in the evolution toward parasitism of Coccidioides spp. © 2014 Muñoz-Hernández et al.; licensee BioMed Central Ltd.
Echegoyen-Carmona R.,Instituto Nacional Of Enfermedades Respiratorias Ismael Cosio Villegas
Revista del Instituto Nacional de Enfermedades Respiratorias | Year: 2012
The aim of this retrospective clinical-epidemiological study is to investigate the causes of an increase in the number of cases with malignant pleural mesotheliom observed at the INER from January 2006 to December 2009. This study comprised 149 in-patients with histopatological diagnose or malignant pleural mesothelioma. Clinical radiographic records were examined considering the following information: genre, age, smoking habits, family history of neoplastic disorders, asbestos exposure, clinical features, laboratory exams, and histological examination of pleural biopsy specimens. Results: An increase of malignant pleural mesothelioma was confirmed amongst INER in-patients. It was most commonly found in male patients. The average age of these patients was between 50-70 years-old. The importance of the immunohistochemical study was confirmed for establishing the diagnosis of the disease of pleural liquid and tumor biopsies. Asbestos was found to be the main cause of this disease. The INER and other Specialized Hospitals where cancer is treated constitute the ultimate link in the Aguilar-Madrid prognoses of an outbreak caused by the transfer to Mexico of manufacturing industries of asbestos-related products that have been banned in Europe, USA, and Canada. Taking into account that this condition is inevitably progressive, the only prevention is to legislate and eliminate asbestos-related industries in Mexico.