Retinoic acid as a modulator of T cell immunity

Indexación: Scopus. DOAJ.Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity.http://www.mdpi.com/2072-6643/8/6/34

TGF-β and MMPs: A complex regulatory loop involved in tumor progression

Transforming growth factor-β (TGF-β) has a dual and contradictory role in cancer. It is a tumor suppressor at early stages of tumor formation by virtue of its growth inhibitory and pro-apoptotic functions. However, at later stages of tumor progression, tumor cells lose their sensitivity to be growth inhibited by this cytokine, and, then, TGF-β facilitates tumor invasion and metastasis by diverse mechanisms, including the induction of an epithelial-mesenchymal transition, the suppression of the immune system and the stimulation of angiogenesis. Matrix metalloproteinases (MMPs) have also been shown to play a pivotal function in tumor cell migration, invasion and angiogenesis. MMPs and TGF-β form an interplay loop that may attenuate or promote tumor progression. On one hand, latent TGF-β, an inactive TGF-β precursor that is sequestered by the extracellular matrix, is proteolytically activated by MMPs; the released active cytokine may, then, suppress or promote tumor cell growth and invasiveness depending on the tumor stage. On the other hand, TGF-β regulates the expression of MMPs and their tissue inhibitors TIMPs in both tumor and stromal cells. MMPs in the tumor microenvironment are involved in the control of tumor cell growth and survival by modulating the bioavailability of growth factors and chemokines, and they also influence inflammation and angiogenesis. Thus, by modulating the net balance of MMPs and TIMPs in both compartments: the tumor and stroma, TGF-β regulates malignant progression.The work developed in our laboratories is supported by grants of the Spanish Ministry of Science and Innovation (grant SAF2010-19152 to MQ) and the Ministry of Science and Technological Development of the Republic of Serbia (grant 175062 to JFS and JK). GC is the recipient of a contract from the Juan de la Cierva program of the Spanish Ministry of Science and Innovation.Peer Reviewe

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

Obesityâ related changes in adipose tissue leukocytes, in particular adipose tissue macrophages (ATMs) and dendritic cells (ATDCs), are implicated in metabolic inflammation, insulin resistance, and altered regulation of adipocyte function. We evaluated stromal cell and white adipose tissue (WAT) expansion dynamics with high fat diet (HFD) feeding for 3â 56 days, quantifying ATMs, ATDCs, endothelial cells (ECs), and preadipocytes (PAs) in visceral epididymal WAT and subcutaneous inguinal WAT. To better understand mechanisms of the early response to obesity, we evaluated ATM proliferation and lipid accumulation. ATMs, ATDCs, and ECs increased with rapid WAT expansion, with ATMs derived primarily from a CCR2â independent resident population. WAT expansion stimulated proliferation in resident ATMs and ECs, but not CD11c+ ATMs or ATDCs. ATM proliferation was unperturbed in Csf2â and Rag1â deficient mice with WAT expansion. Additionally, ATM apoptosis decreased with WAT expansion, and proliferation and apoptosis reverted to baseline with weight loss. Adipocytes reached maximal hypertrophy at 28 days of HFD, coinciding with a plateau in resident ATM accumulation and the appearance of lipidâ laden CD11c+ ATMs in visceral epididymal WAT. ATM increases were proportional to tissue expansion and adipocyte hypertrophy, supporting adipocyteâ mediated regulation of resident ATMs. The appearance of lipidâ laden CD11c+ ATMs at peak adipocyte size supports a role in responding to ectopic lipid accumulation within adipose tissue. In contrast, ATDCs increase independently of proliferation and may be derived from circulating precursors. These changes precede and establish the setting in which largeâ scale adipose tissue infiltration of CD11c+ ATMs, inflammation, and adipose tissue dysfunction contributes to insulin resistance.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142947/1/jlb10097_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142947/2/jlb10097.pd

Ensayo Estructural No Destructivo Utilizando Microtomografía de Rayos X para Estimación de Diferencias de Densidad Másica en Muestras Óseas de Conejo

Al realizarse estudios sobre muestras óseas para analizar características como dureza, densidad y salud, se suelen utilizar equipamientos que permiten la cuantificación de la densidad electrónica, proporcional a la densidad másica, que se relaciona directamente con la densidad mineral ósea. El test conocido como densitometría ósea se suele realizar con equipos de rayos X, ultrasonido o por medio de la utilización de isótopos radioactivos. Este estudio cuantifica la cantidad mineral ósea por superficie y suele ser utilizado para evaluar, entre otros, riesgos de fracturas o estado de osteoporosis. La técnica de tomografía computada utiliza imágenes bidimensionales de rayos X y métodos de reconstrucción tomográfica implementados en algoritmos computacionales para obtener información de la estructura interna de un objeto, de forma no destructiva. Equipamientos especialmente desarrollados logran obtener imágenes con resolución sub-milimétrica, dando lugar a la técnica conocida como micro-tomografía. La posibilidad de estudiar estructuras óseas con este grado de resolución y obtener imágenes morfológicas tridimensionales con información de la densidad electrónica, presenta una importante opción para estudios específicos sobre, entre otros, crecimiento de hueso y estudios de nuevos componentes que permiten acelerar el crecimiento de tejidos dañados. En el presente trabajo se analizan muestras óseas del cráneo de conejos donde se han dañado determinadas zonas y se han injertado diferentes sustancias tendientes a evaluar respuestas de reparación de tejido óseo. El análisis se realiza a los fines de estudiar la performance de la técnica de micro-tomografía desarrollada en laboratorio con el objetivo de observar su potencialidad en este tipo de estudios y la capacidad de estos análisis en la caracterización de las propiedades físicas de este tipo de muestras.publishedVersionFil: Pérez, P. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía, Física y Computación; Argentina.Fil: Pérez, P. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Instituto de Física Enrique Gaviola; Argentina.Fil: Malano, F. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía, Física y Computación; Argentina.Fil: Malano, F. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Instituto de Física Enrique Gaviola; Argentina.Fil: Fernández Bodereau, E. Universidad Nacional de Córdoba, Facultad de Odontología; Argentina.Fil: Dedossi, G. Universidad Nacional de Córdoba, Facultad de Odontología; Argentina.Fil: Figueroa, R. Universidad de La Frontera. Temuco; Chile.Fil: Figueroa, R. Centro de Física e Ingeniería en Medicina. Universidad de La Frontera. Temuco; Chile.Fil: Santibañez, M. Universidad de La Frontera. Temuco; Chile.Fil: Santibañez, M. Centro de Física e Ingeniería en Medicina. Universidad de La Frontera. Temuco; Chile.Fil: Vedelago, J. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía, Física y Computación; Argentina.Fil: Vedelago, J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Instituto de Física Enrique Gaviola; Argentina.Fil: Vedelago, J. Universidad de La Frontera. Temuco; Chile.Fil: Vedelago, J. Centro de Física e Ingeniería en Medicina. Universidad de La Frontera. Temuco; Chile.Fil: Valente, M. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía, Física y Computación; Argentina.Fil: Valente, M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Instituto de Física Enrique Gaviola; Argentina.Fil: Valente, M. Universidad de La Frontera. Temuco; Chile.Fil: Valente, M. Centro de Física e Ingeniería en Medicina. Universidad de La Frontera. Temuco; Chile

Interleukin 17 inhibits myogenic and promotes osteogenic differentiation of C2C12 myoblasts by activating ERK1,2

The present study evaluated the role of interleukin (IL) 17 in multilineage commitment of C2C12 myoblastic cells and investigated associated signaling pathways. The results concerning the effects on cell function showed that IL-17 inhibits the migration of C2C12 cells, while not affecting their proliferation. The data regarding the influence on differentiation demonstrated that IL-17 inhibits myogenic differentiation of C2C12 cells by down-regulating the myogenin mRNA level, myosin heavy chain expression and myotube formation, but promotes their osteogenic differentiation by up-regulating the Runt-related transcription factor 2 mRNA level, cyclooxygenase-2 expression and alkaline phosphatase activity. IL-17 exerted these effects by activating ERK1,2 mitogen activated protein kinase signaling pathway, which in turn regulated the expression of relevant genes and proteins to inhibit myogenic differentiation and induce osteogenic differentiation. Additional analysis showed that the induction of osteogenic differentiation by IL-17 is independent of BMP signaling. The results obtained demonstrate the potential of IL-17 not only to inhibit the myogenic differentiation of C2C12 myoblasts but also to convert their differentiation pathway into that of osteoblast lineage providing new insight into the capacities of IL-17 to modulate the differentiation commitment

Urokinase type plasminogen activator mediates Interleukin-17-induced peripheral blood mesenchymal stem cell motility and transendothelial migration

Mesenchymal stem cells (MSCs) have the potential to migrate toward damaged tissues increasing tissue regeneration. Interleukin-17 (IL-17) is a proinflammatory cytokine with pleiotropic effects associated with many inflammatory diseases. Although IL-17 can modulate MSC functions, its capacity to regulate MSC migration is not well elucidated so far. Here, we studied the role of IL-17 on peripheral blood (PB) derived MSC migration and transmigration across endothelial cells. IL-17 increased PB-MSC migration in a wound healing assay as well as cell mobilization from collagen gel. Concomitantly IL-17 induced the expression of urokinase type plasminogen activator (uPA) without affecting matrix metalloproteinase expression. The incremented uPA expression mediated the capacity of IL-17 to enhance PB-MSC migration in a ERK1,2 MAPK dependent way. Also, IL-17 induced PB-MSC migration alongside with changes in cell polarization and uPA localization in cell protrusions. Moreover, IL-17 increased PB-MSC adhesion to endothelial cells and transendothelial migration, as well as increased the capacity of PB-MSC adhesion to fibronectin, in an uPA-dependent fashion. Therefore, our data suggested that IL-17 may act as chemotropic factor for PB-MSCs by incrementing cell motility and uPA expression during inflammation development

The impact of muscle relaxation techniques on the quality of life of cancer patients, as measured by the FACT-G questionnaire

Introduction Patients with cancer frequently suffer from emotional distress, characterized by psychological symptoms such as anxiety or depression. The presence of psychological symptoms combined with the complex nature of oncology processes can negatively impact patients' quality of life. We aimed to determine the impact of a relaxation protocol on improving quality of life in a sample of oncological patients treated in the Spanish National Public Health System. Materials and methods We conducted a multicenter interventional study without a control group. In total, 272 patients with different oncologic pathologies and showing symptoms of anxiety were recruited from 10 Spanish public hospitals. The intervention comprised abbreviated progressive muscle relaxation training, according to Bernstein and Borkovec. This was followed by weekly telephone calls to each patient over a 1-month period. We collected sociodemographic variables related to the disease process, including information about mental health and the intervention. Patients' quality of life was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. Bivariate and univariate analyses were performed, along with an analysis of multiple correspondences to identify subgroups of patients with similar variations on the FACT-G. Results Patients showed statistically significant improvements on the FACT-G overall score (W = 16806; p<0.001), with an initial mean score of 55.33±10.42 and a final mean score of 64.49±7.70. We also found significant improvements for all subscales: emotional wellbeing (W = 13118; p<0.001), functional wellbeing (W = 16155.5; p<0.001), physical wellbeing (W = 8885.5; p<0.001), and social and family context (W = ?1840; p = 0.037). Conclusions Patients with cancer who learned and practiced abbreviated progressive muscle relaxation experienced improvement in their perceived quality of life as measured by the FACT-G. Our findings support a previous assumption that complementary techniques (including relaxation techniques) are effective in improving the quality of life of patients with cancer

Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like <it>env </it>gene sequences.</p> <p>Results</p> <p>The MMTV-like <it>env </it>gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number <ext-link ext-link-id="AY161347" ext-link-type="gen">AY161347</ext-link>. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the <it>env </it>sequences exhibited disruption of the reading frame due to mutations.</p> <p>Conclusion</p> <p>In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute inflamatory lung infiltrate specimens studied of a Mexican Population.</p

Extremely Long-Lived Stigmas Allow Extended Cross-Pollination Opportunities in a High Andean Plant

High-elevation ecosystems are traditionally viewed as environments in which predominantly autogamous breeding systems should be selected because of the limited pollinator availability. Chaetanthera renifolia (Asteraceae) is an endemic monocarpic triennial herb restricted to a narrow altitudinal range within the high Andes of central Chile (3300–3500 m a.s.l.), just below the vegetation limit. This species displays one of the larger capitulum within the genus. Under the reproductive assurance hypothesis, and considering its short longevity (monocarpic triennial), an autogamous breeding system and low levels of pollen limitation would be predicted for C. renifolia. In contrast, considering its large floral size, a xenogamous breeding system, and significant levels of pollen limitation could be expected. In addition, the increased pollination probability hypothesis predicts prolonged stigma longevity for high alpine plants. We tested these alternative predictions by performing experimental crossings in the field to establish the breeding system and to measure the magnitude of pollen limitation in two populations of C. renifolia. In addition, we measured the stigma longevity in unpollinated and open pollinated capitula, and pollinator visitation rates in the field. We found low levels of self-compatibility and significant levels of pollen limitation in C. renifolia. Pollinator visitation rates were moderate (0.047–0.079 visits per capitulum per 30 min). Although pollinator visitation rate significantly differed between populations, they were not translated into differences in achene output. Finally, C. renifolia stigma longevity of unpollinated plants was extremely long and significantly higher than that of open pollinated plants (26.3±2.8 days vs. 10.1±2.2, respectively), which gives support to the increased pollination probability hypothesis for high-elevation flowering plants. Our results add to a growing number of studies that show that xenogamous breeding systems and mechanisms to increase pollination opportunities can be selected in high-elevation ecosystems