Luiz Stark Aroeira

Hospital La Paz Institute for Health Research

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Rafael Selgas

Hospital Universitario La Paz

Manuel López‐Cabrera

Centro de Biología Molecular Severo Ochoa

M. Auxiliadora Bajo

Hospital Universitario La Paz

Gloria del Peso

Hospital Universitario La Paz

Marta Ruiz‐Ortega

Universidad Autónoma de Madrid

Abelardo Aguilera

Hospital Universitario de La Princesa

Alberto Ortíz

Hospital Universitario Fundación Jiménez Díaz

Guadalupe Tirma Gónzalez-Mateo

Centro de Biología Molecular Severo Ochoa

Marı́a Luisa Lozano

Centro Regional de Hemodonación

José A. Jiménez‐Heffernan

Hospital Universitario de La Princesa

Cooperative Institutions

Hospital Universitario La Paz

Universidad Autónoma de Madrid

University of Thessaly

Okayama University

Ege University

Academic Medical Center

Dong-A University

Instituto de Salud Carlos III

Hospital Universitario de La Princesa

Başkent University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Hydroxyurea before oral antigen blocks the induction of oral tolerance.

PubMed (1993)

Luiz Stark Aroeira Cláudia R. Carvalho José Mengel Giancarlo A. Garcia N.M. Vaz

1. Treatment with hydroxyurea (HU, 1 mg/g ip, 2 doses applied 7 h apart) eliminates the majority of cells undergoing mitosis (cycling cells) without affecting non-cycling cells. Oral tolerance, induced by a single gavage with 20 mg of ovalbumin, results in a drastic inhibition of anti-Ova antibody responses in young adult mice. Oral tolerance is actively maintained by the presence of specific suppressor T cells which may adoptively transfer the tolerance to naive syngeneic recipients. Under the clonal selection hypothesis, the induction of oral tolerance should be blocked by HU treatment applied soon after oral exposure to the antigen by the elimination of specific clones of lymphocytes activated by tolerogenic presentation of the antigen. 2. However, treatment with HU initiated 3, 6 or 24 h after oral exposure to ovalbumin had no effect on the induction of oral tolerance in B6D2F1 mice. However, treatment with HU 24 h before antigen exposure, totally blocked the induction of tolerance. Treatment with HU 72 h before ovalbumin had no effect. 3. In animals treated with HU 24 h before, the adoptive transfer of normal thymus, bone marrow or spleen cells partially restored the susceptibility to the induction of oral tolerance. 4. The results suggest that cycling cells, which may be totally regenerated within 72 h after treatment with HU, and are present in normal thymus, bone marrow and spleen, are crucially important for the induction of oral tolerance.

Adoptive Cell Transfer

Oral tolerance

Source

Cite

Citations (2)

Citrin deficiency: Early severe cases in a European country

Clinics and Research in Hepatology and Gastroenterology (2020)

Lorena Fernández Tomé Luiz Stark Aroeira Gema Muñoz Bartolo Ángela de la Vega Bueno C. Camarena Grande

10.1016/j.clinre.2020.101595

Cite

Citations (4)

H-ras and N-ras are dispensable for T-cell development and activation but critical for protective Th1 immunity

Blood (2011)

Salvador Iborra Manuel Soto Luiz Stark Aroeira Esther Castellano Balbino Alarcón

Thymocyte

Priming (agriculture)

10.1182/blood-2010-10-315770

Cite

Citations (41)

CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

Journal of the American Society of Nephrology (2009)

Elsa Sánchez‐López Sandra Rayego‐Mateos Raquel Rodrigues‐Díez Javier Sánchez Rodriguez Raúl R. Rodrigues-Díez

Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-kappaB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-kappaB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-gamma, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-kappaB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-kappaB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-kappaB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-kappaB pathway.

Proinflammatory cytokine

10.1681/asn.2008090999

Cite

Citations (117)

Treatment with Natalizumab in Relapsing–Remitting Multiple Sclerosis Patients Induces Changes in Inflammatory Mechanism

Journal of Clinical Immunology (2011)

Jaime Ramos‐Cejudo Celia Oreja‐Guevara Luiz Stark Aroeira Luis Rodríguez de Antonio Beatriz Chamorro

Natalizumab is a widely accepted drug for the relapsing-remitting subtype of multiple sclerosis (RRMS). The present longitudinal exploratory study in RRMS patients analyzes the effects of natalizumab treatment on the levels of pro-inflammatory and anti-inflammatory cytokine protein levels and also the frequency and suppressor function of regulatory T cells. Flow cytometry was used to determine cytokines and regulatory T cell frequency while regulatory T cell suppressor function was assayed in vitro at different time-points after starting with natalizumab. Results showed serum levels of pro-inflammatory interferon gamma and interleukin (IL)-12p70, as well as anti-inflammatory IL-4 and IL-10, were elevated just a few hours or days after first IV infusion of natalizumab. Interestingly, other cytokines like IL-5 or IL-13 were also elevated while pro-inflammatory IL-17, IL-2, and IL-1β increased only after a long-term treatment, suggesting different immune mechanisms. In contrast, we did not observe any effect of natalizumab treatment on regulatory T cell frequency or activity. In conclusion, these results suggest natalizumab has other immunological effects beyond VLA-4 interaction and inhibition of CNS extravasation, the relevance of which is as yet unknown and warrants further investigation.

Natalizumab

Proinflammatory cytokine

10.1007/s10875-011-9522-x

Cite

Citations (50)

A natural anti-T-cell receptor monoclonal antibody protects against experimental autoimmune encephalomyelitis

Journal of Neuroimmunology (2011)

Edgar Fernández-Malavé Luiz Stark Aroeira

Encephalomyelitis

10.1016/j.jneuroim.2011.02.006

Cite

Citations (3)

Mesenchymal Conversion of Mesothelial Cells as a Mechanism Responsible for High Solute Transport Rate in Peritoneal Dialysis: Role of Vascular Endothelial Growth Factor

American Journal of Kidney Diseases (2005)

Luiz Stark Aroeira Abelardo Aguilera Rafael Selgas Marta Ramírez‐Huesca Marı́a Luisa Lozano

Mesothelium

10.1053/j.ajkd.2005.08.011

Cite

Citations (200)

TGF-Beta Blockade Increases Renal Inflammation Caused by the C-Terminal Module of the CCN2

Mediators of Inflammation (2015)

Raquel Rodrigues‐Díez Sandra Rayego‐Mateos Macarena Orejudo Luiz Stark Aroeira Rafael Selgas

The CCN family member 2 (CCN2, also known as connective tissue growth factor) may behave as a risk biomarker and a potential therapeutic target for renal disease. CCN2 participates in the regulation of inflammation and fibrosis. TGF- β is considered the main fibrogenic cytokine; however, in some pathological settings TGF- β also has anti-inflammatory properties. CCN2 has been proposed as a downstream profibrotic mediator of TGF- β , but data on TGF- β role in CCN2 actions are scarce. Our aim was to evaluate the effect of TGF- β blockade in CCN2-mediated experimental renal damage. Systemic administration of the C-terminal module of CCN2 to mice caused sustained renal inflammation. In these mice, TGF- β blockade, using an anti-TGF- β neutralizing antibody, significantly increased renal expression of the NGAL (a kidney injury biomarker), kidney infiltration by monocytes/macrophages, and upregulation of MCP-1 expression. The anti-inflammatory effect of TGF- β seems to be mediated by a dysregulation of the systemic Treg immune response, shown by decreased levels of circulating CD4 + /Foxp3 + Treg cells. Our experimental data support the idea that TGF- β exerts anti-inflammatory actions in the kidney and suggest that it is not an optimal therapeutic target.

10.1155/2015/506041

Cite

Citations (16)

Anti-Vβ8 antibodies induce and maintain staphylococcal enterotoxin B-triggered Vβ8+ T cell anergy

European Journal of Immunology (1999)

Luiz Stark Aroeira Concepción G. Mouton José Luis Torán E. Sally Ward Carlos Martínez‐A

The mechanism involved in the maintenance of staphylococcal enterotoxin B (SEB)-induced T cell anergy is poorly understood. We demonstrated earlier that B cells play an important role in the maintenance of SEB-induced T cell anergy in vivo and in vitro. Here, we demonstrate that B cells are not essential in SEB-induced T cell activation, but are important for the maintenance of T cell memory phenotype and anergy in vivo. Studying the activated B cell repertoire, we observe that SEB treatment increases serum anti-Vβ8 antibody titer as detected by enzyme-linked immunosorbent assay using soluble Vβ8 chains as antigens, and by staining of a Vβ8-expressing thymoma. These antibodies disappear gradually after immunization with SEB, whereas the capacity of the T cells to respond to SEB in vitro is restored. Anti-Vβ8 monoclonal antibody treatment causes Vβ8+ T cell unresponsiveness to SEB in vitro (anergy), without affecting CD4Vβ8+ T cell frequency. Together, these results suggest a new mechanism to explain the maintenance of SEB-induced T cell anergy, which is dependent on B cells and on anti-Vβ8 antibody that specifically interacts with Vβ8+ T cells.

Clonal anergy

Superantigen

10.1002/(sici)1521-4141(199902)29:02<437::aid-immu437>3.3.co;2-1

Cite

Citations (0)

A Nanoconjugate Apaf-1 Inhibitor Protects Mesothelial Cells from Cytokine-Induced Injury

PLoS ONE (2009)

Beatriz Santamaría Alberto Benito‐Martín Álvaro C. Ucero Luiz Stark Aroeira Ana Reyero

Inflammation may lead to tissue injury. We have studied the modulation of inflammatory milieu-induced tissue injury, as exemplified by the mesothelium. Peritoneal dialysis is complicated by peritonitis episodes that cause loss of mesothelium. Proinflammatory cytokines are increased in the peritoneal cavity during peritonitis episodes. However there is scarce information on the modulation of cell death by combinations of cytokines and on the therapeutic targets to prevent desmesothelization.Human mesothelial cells were cultured from effluents of stable peritoneal dialysis patients and from omentum of non-dialysis patients. Mesothelial cell death was studied in mice with S. aureus peritonitis and in mice injected with tumor necrosis factor alpha and interferon gamma. Tumor necrosis factor alpha and interferon gamma alone do not induce apoptosis in cultured mesothelial cells. By contrast, the cytokine combination increased the rate of apoptosis 2 to 3-fold over control. Cell death was associated with the activation of caspases and a pancaspase inhibitor prevented apoptosis. Specific caspase-8 and caspase-3 inhibitors were similarly effective. Co-incubation with both cytokines also impaired mesothelial wound healing in an in vitro model. However, inhibition of caspases did not improve wound healing and even impaired the long-term recovery from injury. By contrast, a polymeric nanoconjugate Apaf-1 inhibitor protected from apoptosis and allowed wound healing and long-term recovery. The Apaf-1 inhibitor also protected mesothelial cells from inflammation-induced injury in vivo in mice.Cooperation between tumor necrosis factor alpha and interferon gamma contributes to mesothelial injury and impairs the regenerative capacity of the monolayer. Caspase inhibition attenuates mesothelial cell apoptosis but does not facilitate regeneration. A drug targeting Apaf-1 allows protection from apoptosis as well as regeneration in the course of inflammation-induced tissue injury.

Mesothelium

Proinflammatory cytokine

10.1371/journal.pone.0006634

Cite

Citations (38)