Tuftsin – Properties and Analogs

Siebert, Agnieszka; Gensicka-Kowalewska, Monika; Cholewiński, Grzegorz; Dzierzbicka, Krystyna

doi:10.2174/0929867324666170725140826

Cited by 35 publications

(27 citation statements)

References 65 publications

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“…TPC was synthesized to create a new small molecule that would modulate the immune response. The approach we have taken in harnessing the immunomodulatory molecules found in helminths and their ova, together with that of self-peptide, could be a breakthrough in the field of autoimmune treatments [11,12,39,40].…”

Section: Discussionmentioning

confidence: 99%

“…It can be recognized by receptors on monocytes and macrophages and has immunomodulatory properties [11,12]. It can be recognized by receptors on monocytes and macrophages and has immunomodulatory properties [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…In 1970, Najjar and Nishioka were the first to define tuftsin, an endogenous tetrapeptide (Thr-Lys-Pro-Arg) released during enzymatic cleavage of the Fc heavy chain of immunoglobulin IgG in the spleen. It can be recognized by receptors on monocytes and macrophages and has immunomodulatory properties [11,12]. Accordingly, we conjugated non-immunogenic PC with the self-natural immunomodulatory adjuvant, tuftsin, and created tuftsinphosphorylcholine (TPC).…”

Section: Introductionmentioning

confidence: 99%

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Tuftsin–phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model

Shemer

Kivity

Shovman

et al. 2018

Clinical and Experimental Immunology

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The role of helminth treatment in autoimmune diseases is growing constantly. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with challenging treatment options. Tuftsin-phosphorylcholine (TPC) is a novel helminth-based compound that modulates the host immune network. This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first-line therapy for SLE: corticosteroids (methylprednisolone). Lupus-prone NZBxW/F mice were treated with TPC (5 µg/mouse), methylprednisolone (MP; 5 mg/body weight) or phosphate-buffered saline (PBS) (control) three times per week once glomerulonephritis, defined as proteinuria of grade > 100 mg/dl, was established. Levels of anti-dsDNA autoantibodies were evaluated by enzyme-linked immunosorbent assay (ELISA), splenic cytokines were measured in vitro and the kidney microscopy was analysed following staining. TPC and MP treatments improved lupus nephritis significantly and prolonged survival in NZBxW/F mice. TPC-treated mice showed a significantly decreased level of proteinuria (P < 0·001) and anti-dsDNA antibodies (P < 0·001) compared to PBS-treated mice. Moreover, TPC and MP inhibited the production of the proinflammatory cytokines interferon IFN-γ, interleukin IL-1β and IL-6 (P < 0·001) and enhanced expression of the anti-inflammatory cytokine IL-10 (P < 0·001). Finally, microscopy analysis of the kidneys demonstrated that TPC-treated mice maintained normal structure equally to MP-treated mice. These data indicate that the small molecule named TPC hinders lupus development in genetically lupus-prone mice equally to methylprednisolone in most of the cases. Hence, TCP may be employed as a therapeutic potential for lupus nephritis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tuftsin–phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model

Shemer

Kivity

Shovman

et al. 2018

Clinical and Experimental Immunology

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“…TPC (tuftsin-phosphorylcholine) is a small synthetic molecule based on helminth-derived products, composed of tuftsin-phosphorylcholine conjugate. The PC is a non-immunogenic, natural small molecule, while tuftsin is a physiological tetrapeptide (Thr-Lys-Pro-Arg) fraction of the IgG heavy chain molecule produced by enzymatic cleavage of the Fc domain of the IgG heavy chain in the spleen [18,19]. Tuftsin stimulates phagocytosis and has other stimulatory effects, including increased migration and activation of macrophages and enhanced chemotaxis of monocytes [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

“…The PC is a non-immunogenic, natural small molecule, while tuftsin is a physiological tetrapeptide (Thr-Lys-Pro-Arg) fraction of the IgG heavy chain molecule produced by enzymatic cleavage of the Fc domain of the IgG heavy chain in the spleen [18,19]. Tuftsin stimulates phagocytosis and has other stimulatory effects, including increased migration and activation of macrophages and enhanced chemotaxis of monocytes [18][19][20][21]. It has been used also as a natural adjuvant in the development of an influenza vaccine without side effects [18,19,22].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulation of Murine Chronic DSS-Induced Colitis by Tuftsin–Phosphorylcholine

Shor

Lachnish

Bashi

et al. 2019

JCM

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Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin–phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1β, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.

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Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Baranyai

Soria‐Carrera

Alleva

et al. 2020

Advanced Therapeutics

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The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial‐loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment.

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Tuftsin – Properties and Analogs

Cited by 35 publications

References 65 publications

Tuftsin–phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model

Tuftsin–phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model

Immunomodulation of Murine Chronic DSS-Induced Colitis by Tuftsin–Phosphorylcholine

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

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