The New Salicylate Derivative UR-1505 Modulates the Th2/Humoral Response in a Dextran Sodium Sulphate Model of Colitis That Resembles Ulcerative Colitis

Bailón, Elvira; Román, Juan; Ramis, Isabel; Michelena, Pedro; Balsa, Dolors; Zarzuelo, Antonio; Gálvez, Júlio; Comalada, Mònica

doi:10.1254/jphs.08292sc

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…UR-1505 inhibits αCD3/CD28-induced, but not JAK/STAT-induced T cell proliferation and IL-5 as well as IFNγ expression. UR-1505 shows anti-inflammatory properties in rat colitis models [ 134 ]. Triflusal , another salicylic acid derivative, inhibits not only NFATc-DNA complex formation, but additionally NF-κB activation [ 135 ].…”

Section: Small Molecular Inhibitorsmentioning

confidence: 99%

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

Sieber

Baumgrass

2009

Cell Commun Signal

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The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question -whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway -alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects.

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Section: Small Molecular Inhibitorsmentioning

confidence: 99%

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

Sieber

Baumgrass

2009

Cell Commun Signal

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“…Calcineurin inhibitors, such as cyclosporine A (CsA) and tacrolimus (FK506), have been used to treat graft rejection and autoimmune diseases, including atopic dermatitis, rheumatoid arthritis, and lupus nephritis ( 27 – 32 ). More inhibitors specifically targeting NFATs (such as VIVIT peptide, INCA-1, ST-1959, and UR-1505) were developed and are being verified; however, they are yet to be analyzed in suitable animal models of autoimmune diseases to investigate their potential of ameliorating diseases ( 33 – 36 ).…”

Section: Introduction: Classical Nfatsmentioning

confidence: 99%

Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases

2018

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The nuclear factor of activated T cells (NFAT) family of transcription factors, which includes NFAT1, NFAT2, and NFAT4, are well-known to play important roles in T cell activation. Most of NFAT proteins are controlled by calcium influx upon T cell receptor and costimulatory signaling results increase of IL-2 and IL-2 receptor. NFAT3 however is not shown to be expressed in T cells and NFAT5 has not much highlighted in T cell functions yet. Recent studies demonstrate that the NFAT family proteins involve in function of lineage-specific transcription factors during differentiation of T helper 1 (Th1), Th2, Th17, regulatory T (Treg), and follicular helper T cells (Tfh). They have been studied to make physical interaction with the other transcription factors like GATA3 or Foxp3 and they also regulate Th cell signature gene expressions by direct binding on promotor region of target genes. From last decades, NFAT functions in T cells have been targeted to develop immune modulatory drugs for controlling T cell immunity in autoimmune diseases like cyclosporine A, FK506, etc. Due to their undesirable side defects, only limited application is available in human diseases. This review focuses on the recent advances in development of NFAT targeting drug as well as our understanding of each NFAT family protein in T cell biology. We also discuss updated detail molecular mechanism of NFAT functions in T cells, which would lead us to suggest an idea for developing specific NFAT inhibitors as a therapeutic drug for autoimmune diseases.

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“…These findings provided two new insights into the pathogenesis of IBD at that time: the first one is that a genetic factor lead to mucosal inflammation that resembles IBD and the second one is that altered immune responses contribute to the initiation and chronification of IBD. The most widely used IBD animal models are colitis chemically induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) (10), oxazolone (11), and dextran sodium sulfate (DSS) (12,13) (Table 1). Importantly, transfer of a T cell population (CD4 + CD45RB high T cells) that lacks regulatory T cells into scid or Rag −/− animals induced colonic inflammation (14) ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-19 Is a Negative Regulator of Innate Immunity and Critical for Colonic Protection

et al. 2011

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Abstract. The cytokine, interleukin (IL)-19, is a member of the IL-10 family that includes . Recent studies have shown that IL-19 is produced by keratinocytes, epithelial cells, macrophages, and B-cells. Little is known about the exact biological role of IL-19 in immunological regulation, although there is an increasing body of data demonstrating that IL-19 is associated with the development of Th2 responses and the pathogenesis of psoriasis. In this review, I shall attempt to discuss current knowledge about the role of IL-19 on macrophages and the potential role in inflammatory bowel disease.

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The New Salicylate Derivative UR-1505 Modulates the Th2/Humoral Response in a Dextran Sodium Sulphate Model of Colitis That Resembles Ulcerative Colitis

Cited by 6 publications

References 15 publications

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases

Interleukin-19 Is a Negative Regulator of Innate Immunity and Critical for Colonic Protection

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