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Featured researches published by Ariel Werman.


Proceedings of the National Academy of Sciences of the United States of America | 2007

Antiviral and immunoregulatory activities of IFN-γ depend on constitutively expressed IL-1α

Vladimir Hurgin; Daniela Novick; Ariel Werman; Charles A. Dinarello; Menachem Rubinstein

IFN-γ induces its immunoregulatory activities by activating genes mainly through the Jak-STAT signaling pathway. Here we show that what was considered to be intrinsic IFN-γ activities depend largely on the basal level of NF-κB, which is maintained by constitutively expressed IL-1α. The IL-1 receptor antagonist and antibodies to IL-1α, but not to IL-1β, inhibited the antiviral activity of IFN-γ by 90%, whereas no inhibition of type I IFN activity was observed. Similarly, the induction of many genes by IFN-γ, including HLA-DR, ICAM-1, IL-18BP, and genes mediating its antiviral activity, greatly depended on basal IL-1α. Furthermore, IFN-γ induced serum IL-18 binding protein in wild-type mice but not in IL-1α/β double-deficient mice. Thus, constitutively expressed IL-1α is critical for numerous IFN-γ activities.


Clinical Nephrology | 2004

Effect of advanced glycation end products on endotoxin-induced TNF-alpha, IL-1beta and IL-8 in human peripheral blood mononuclear cells.

Leonid L. Reznikov; Waksman J; Tania Azam; Soo Hyun Kim; Philip Bufler; Toshimitsu Niwa; Ariel Werman; Xiaohong Zhang; Monika Pischetsrieder; Stanley Shaldon; Charles A. Dinarello

BACKGROUND/AIMS Advanced glycated end products (AGE) are endogenous proteins that have formed covalent complexes with sugars by a nonenzymatic process. Being proinflammatory molecules, AGE are thought to contribute to chronic systemic and local inflammatory processes associated with pathological changes in various diseases. In patients with end-stage renal disease, AGE are believed to play a role in the progression of atherosclerosis and worsening of renal failure. In patients receiving hemodialysis, AGE are thought to contribute to the inflammatory components of the therapy, particularly in diabetic patients. METHODS In the present study, AGE were produced using 5% human serum albumin (HSA) and 50% glucose, both used for intravenous infusion into humans and both released after strict control for endotoxin content. The presence of AGE formed by HSA and glucose was confirmed using 2 independent assays. The inflammatory properties of these AGE were assessed using synthesis and release of the proinflammatory cytokines interleukin-1 (IL-1), tumor necrosis factor (TNF) and IL-8, a chemokine. RESULTS Alone, AGE did not induce these cytokines from peripheral blood mononuclear cells (PBMC) obtained from 14 healthy human donors. However, in the presence of 1 or 10 ng/ml of endotoxin, AGE augmented the production of IL-1 and TNF above that induced by endotoxin alone. Although the amount of augmentation of LPS-induced cytokines by AGE varied between the blood donors, the response was consistently observed and reached statistical significance. The augmentation of cytokine production was confirmed using AGE prepared with different lots of HSA and glucose. CONCLUSION These results demonstrate that in the strict absence ofendotoxins, AGE are formed that do not stimulate cytokine production from PBMC of healthy donors, however, AGE significantly augment the synthesis and release of proinflammatory cytokine in the presence of low concentrations of endotoxins. The data suggest that renal replacement therapies should consider the role of microbial products in potentiating the biological consequences of naturally formed AGE and their potential to contribute to systemic and local inflammation in renal replacement therapies. Therefore, although the formation of AGE is unavoidable, excluding microbial products during renal replacement therapy should reduce the pathological consequences of AGE.


Proceedings of the National Academy of Sciences of the United States of America | 2004

The precursor form of IL-1alpha is an intracrine proinflammatory activator of transcription

Ariel Werman; Rachel Werman-Venkert; Rosalyn M. White; Jaekwon Lee; Batsheva Werman; Yakov Krelin; Elena Voronov; Charles A. Dinarello; Ron N. Apte


Atherosclerosis | 2007

Differential role and tissue specificity of interleukin-1α gene expression in atherogenesis and lipid metabolism

Yehuda Kamari; Rachel Werman-Venkert; Aviv Shaish; Ariel Werman; Ayelet Harari; Ayelet Gonen; Elena Voronov; Itamar Grosskopf; Yehonatan Sharabi; Ehud Grossman; Yoichiro Iwakura; Charles A. Dinarello; Ron N. Apte; Dror Harats


Archive | 2002

Opposing Effects of IL-1α and IL-1β on Malignancy Patterns

Ron N. Apte; Tatyana Dvorkin; Xiaoping Song; Eyal Fima; Yakov Krelin; Alon Yulevitch; Reuven Gurfinkel; Ariel Werman; Rosalyn M. White; Shmuel Argov; Yacob Shendler; Olle Bjorkdahl; Mikael Dohlsten; Margot Zöller; Shraga Segal; Elena Voronov


PLOS ONE | 2010

Correction: C/EBP-β Regulates Endoplasmic Reticulum Stress–Triggered Cell Death in Mouse and Human Models.

Ofir Meir; Efrat Dvash; Ariel Werman; Menachem Rubinstein


Archive | 2008

Glycan modified soluble receptors and binding protein and their use

Menachem Rubinstein; Ariel Werman; Ben Alkahe


Archive | 2009

Method for inhibiting release of hepatitis B virus from liver cells

Menachem Rubinstein; Ariel Werman; Ben Alkahe


Archive | 2008

Récepteurs solubles à modification glycane et protéines de liaison à modification glycane et leur utilisation

Menachem Rubinstein; Ariel Werman; Ben Alkahe


Archive | 2008

Binding proteins and soluble receptors modified glycans and their use

Menachem Rubinstein; Ariel Werman; Ben Alkahe

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Menachem Rubinstein

Weizmann Institute of Science

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Elena Voronov

Ben-Gurion University of the Negev

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Ron N. Apte

Ben-Gurion University of the Negev

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Ben Alkahe

Weizmann Institute of Science

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Charles A. Dinarello

University of Colorado Denver

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Rachel Werman-Venkert

Ben-Gurion University of the Negev

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Alon Yulevitch

Ben-Gurion University of the Negev

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