Cetirizine and allopurinol as novel weapons against cellular autoimmune disorders

Namazi, Mohammad Reza

doi:10.1016/j.intimp.2004.01.022

Cited by 43 publications

(25 citation statements)

References 38 publications

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“…High levels of UA in blood also frequently occur in patients with psoriasis due to extensive skin damage, and psoriasis is thought to exhibit a mixed Th1/Th17 pathology (34). Moreover, allopurinol, traditionally used to treat hyperuricemia in gout by lowering uric acid levels in the blood, has also shown efficacy in the treatment of other disorders, including autoimmune uveitis and inflammatory bowel diseases (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Uric Acid-Driven Th17 Differentiation Requires Inflammasome-Derived IL-1 and IL-18

Conforti-Andreoni

Spreafico

Qian

et al. 2011

The Journal of Immunology

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Uric acid is released from damaged cells and serves as a danger signal that alerts the immune system to potential threats, even in the absence of microbial infection. Uric acid modulation of innate immune responses has been extensively studied, but the impact of this damage-associated molecular pattern on adaptive responses remains largely unknown. In this study, we report that, in the presence of NF-κB signaling, uric acid crystals were capable of stimulating dendritic cells to promote the release of cytokines associated with Th17 polarization. Accordingly, naive CD4+ T cells cocultured with uric acid-treated dendritic cells differentiated toward the Th17 lineage. Th17 differentiation required the inflammasome-dependent cytokines IL-1α/β and IL-18 in both in vitro and in vivo models, and the inflammasome adaptor protein ASC and caspase-1 were essential for Th17 responses. Collectively, our findings indicate a novel role for the danger signal uric acid, in cooperation with NF-κB activation, in driving proinflammatory Th17 differentiation. Our data indicate that sterile inflammation shapes adaptive immunity, in addition to influencing early innate responses.

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Section: Discussionmentioning

confidence: 99%

Uric Acid-Driven Th17 Differentiation Requires Inflammasome-Derived IL-1 and IL-18

Conforti-Andreoni

Spreafico

Qian

et al. 2011

The Journal of Immunology

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“…Activated T cells proliferate, differentiate, and produce type 1 cytokines including IL-2, IL-12, IFNγ, and TNFα or type 2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) (Bullens et al, 2004;Namazi, 2004;Luongo et al, 2006). IFNα is involved in the regulation of nearly all phases of the immune and inflammatory responses, including the activation and differentiation of lymphocytes, macrophages, and others (Gattoni et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have suggested that the alterations of cytokine production could be a useful biomarker for environmental pollutant exposure (Camacho et al, 1999;Hooghe et al, 2000;Yang et al, 2000;Berek et al, 2001;Yang et al, 2001;Yang et al, 2002;Calemine et al, 2003;Devos et al, 2003;Devos et al, 2004;Luongo et al, 2006;Fairley et al, 2007). Thus, in order to evaluate the quantitative changes of cytokines after ATZ, PFOA and ZEA exposure, we investigated the changes in the interferon gamma (IFNγ, type 1 cytokine), tumor necrosis factor-alpha (TNFα, type 1 cytokine) and interleukin-5 (IL-5, type 2 cytokine) (Hooghe et al, 2000;Bullens et al, 2004;Namazi, 2004) levels after EDs exposure in Jurkat cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of Atrazine, Perfluorooctanoic Acid and Zearalenone on IFNγ, TNFα, and IL-5 mRNA Expression in Jurkat Cells

Lee¹,

Son²,

Yoon³

et al. 2010

Biomolecules and Therapeutics

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-Cytokine production is a sensitive indicator for monitoring perturbations of the immune system by xenobiotics in animals and humans. In the present study, we evaluated the changes in IFNγ, IL-5 and TNFα mRNA expression after atrazine (ATZ), perfluorooctanoic acid (PFOA) or zearalenone (ZEA) exposure in Jurkat cells. The IC50 (concentration for a 50% inhibition of cell proliferation) of PFOA and ZEA after 3 days culture were 226.6 μM and 52.6 μM, respectively. The effects of ATZ on cytokine expression followed in increasing order of IFNγ＞IL-5＞TNFα at 3 μM and at the lower concentrations the degree of effects on three cytokines were less clear between the cytokines when compared to control level. PFOA had marked increasing effect in order of IFNγ＞TNFα＞IL-5 mRNA expression at IC50, and these patterns were continued at the lower concentrations, IC50/2 and IC50/4. ZEA caused the overexpression of cytokine mRNAs in order of IL-5＞IFNγ＞TNFα at both IC50 and IC50/2, and at IC50/4 the overexpression order was IL-5＞TNFα. On other hand, IFNγ was less distinct compared to the control. These data indicate that ATZ, PFOA and ZEA caused the overtranscription of IFNγ, IL-5 and TNFα mRNA, and the overproduction of these cytokines may eventually lead to immune disorders.

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“…Current evidence indicates that purine analogues alone or in combination with other chemotherapeutic agents are very effective against almost any fast-growing cells (22,41). Allopurinol, a purine analogue, has been used to treat leishmaniasis alone (34,48) or combined with other drugs (21,35,36,39,47).…”

Section: Discussionmentioning

confidence: 99%

Purine Nucleobase Transport in Amastigotes of Leishmania mexicana : Involvement in Allopurinol Uptake

Al-Salabi

Koning

2005

Antimicrob Agents Chemother

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Nucleobase and nucleoside transporters play central roles in the biochemistry of parasitic protozoa, as they lack the ability to synthesize purines de novo and are absolutely reliant upon purine salvage from their hosts. Furthermore, such transporters are potentially critical to the pharmacology of these important human pathogens, because they mediate the uptake of purine analogues, as well as some nonpurine drugs, that can be selectively cytotoxic to the parasites. We here report the first identification and characterization of a purine nucleobase transporter in Leishmania amastigotes. Uptake of [ 3 H]hypoxanthine by Leishmania mexicana amastigotes was mediated by a single high-affinity transporter, LmexNBT1, with a K m of 1.6 ؎ 0.4 M and high affinity for adenine, guanine, and xanthine but low affinity for nucleosides and pyrimidine nucleobases. Allopurinol, an antileishmanial hypoxanthine analogue, was apparently taken up by the same transporter. Using Parasitic protozoa of the genus Leishmania are the etiological agents of leishmaniasis. Some 12 million people throughout the world suffer from leishmaniasis, ranging from the disfiguring cutaneous form to often-fatal visceral leishmaniasis. Leishmania species are sandfly-transmitted protozoan parasites. The life cycle is divided into promastigotes and metacyclics in the insect vectors and amastigotes in their mammalian hosts, which are responsible for all clinical manifestations.Most of the currently available antileishmanial drugs have been discovered empirically, as until recently insufficient information was known about the biochemistry, physiology, and molecular biology of these parasites and the interactions with their hosts (23). The limitations of the current treatment for leishmaniasis, as a result of drug resistance and the severe side effects of most of the existing therapeutic agents, and the urgent need for new therapeutic approaches, are well documented (12,56,60).The development of a rational therapeutic strategy for the treatment and prevention of parasitic disease depends on exploitation of fundamental biochemical disparities between parasite and host, such as the inability of protozoan parasites to synthesize purines de novo (5). Current antiprotozoal agents often derive selectivity from selective accumulation by the parasite rather than the host cell (15). The selectivity and the efficacy of purine antimetabolites can be achieved by the cell surface transporters that mediate access to the cell, as substrate recognition by nucleobase transporters is strikingly different in humans and kinetoplastids such as Trypanosoma brucei (58) and Leishmania major promastigotes (2). Purine and pyrimidine antimetabolites have been highly successful against many viral infections as well as malignancies (27) and show great promise against protozoal infections as well (reviewed in references 14, 17, and 23). Allopurinol, a purine nucleobase analogue, is clinically used against various manifestations of leishmaniasis (1,13,39).Whereas purine transporters in prom...

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Cetirizine and allopurinol as novel weapons against cellular autoimmune disorders

Cited by 43 publications

References 38 publications

Uric Acid-Driven Th17 Differentiation Requires Inflammasome-Derived IL-1 and IL-18

Uric Acid-Driven Th17 Differentiation Requires Inflammasome-Derived IL-1 and IL-18

Effect of Atrazine, Perfluorooctanoic Acid and Zearalenone on IFNγ, TNFα, and IL-5 mRNA Expression in Jurkat Cells

Purine Nucleobase Transport in Amastigotes of Leishmania mexicana : Involvement in Allopurinol Uptake

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