Therapeutic Toll-like receptor agonists directly influence mouse and human T cell lymphoma cell viability and cytokine secretion

Landrigan, Angela; Yiu, Gloria; Agarwal, Kanika; Utz, Paul J.

doi:10.3109/10428194.2011.606944

Cited by 3 publications

(5 citation statements)

References 18 publications

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“…No significant reduction in cell viability was observed when comparing treated cells vs non-treated controls. Previous studies have demonstrated that CpG, even at high concentrations (6 μM), does not alter the viability of human cells [ 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

“…Immunomodulators were added at concomitantly with promastigotes to achieve concentrations of 100, 200 and 300 μM pentoxifylline and 2.5, 5, 10 μM CpG ODN 2006; anti-leishmanial drugs were added 24 h after infection. The concentration ranges of immunomodulators were based on prior exploratory experiments to evaluate the effect of pentoxifylline on TNF-α secretion and, previous investigations of CpG ODN 2006 in the in vitro immune response of human PBMCs [ 32 , 33 ]. Parasite burden and cytokine secretion were evaluated at 120 h of culture, and 96 h after addition of anti-leishmanial drugs.…”

Section: Methodsmentioning

confidence: 99%

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Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

et al. 2015

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BackgroundTherapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses.MethodologyTo achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays.Principal FindingsAnti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine antimoniate. However, pentoxifylline diminished secretion of TNF-α, IFN-γ and IL-13, cytokines associated with the outcome of infection by species of the Viannia subgenus. Exposure to CpG diminished the leishmanicidal effect of meglumine antimoniate, but not miltefosine, and significantly reduced secretion of IL -10, alone and in combination with either antileishmanial drug. IL-13 increased in response to CpG plus miltefosine.Conclusions and SignificanceHuman PBMCs allow integrated ex vivo assessment of antileishmanial treatments, providing information on host and parasite determinants of therapeutic response that may be used to tailor therapeutic strategies to optimize clinical resolution.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

et al. 2015

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“…The biological meaning of the low but significant decrease in IL3 remains unexplained. All references were in supporting information P02778 637 43 14.9 ** ↑ in blood [16] and skin [10,11] Involved in the preferential infiltration of T cells (CD4 + ) CCL27 (C-TACK) Q9Y4X3 811 88 9.2 ** ↑ in blood [17][18][19] and skin [17] Recruitment of atypical T cells to the skin CXCL9 (Mig) Q07325 424 50 8.4 ** ↑ in skin [11] Involved in the preferential infiltration of activated T cells [20] and cell lines [21] Chemoattractant involved in epidermotropism of T cells [9] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation, B-cell maturation and proliferation, and fibroblast growth factor activity…”

Section: Paul Fogelmentioning

confidence: 99%

Proteomic analysis of stratum corneum in Cutaneous T‐Cell Lymphomas and psoriasis

Méhul

Ménigot

Fogel³

et al. 2019

Experimental Dermatology

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Stratum corneum collected by tape stripping from 10 and 24 subjects with cutaneous T‐cell lymphomas (CTCL) or psoriasis, respectively, were compared using quantitative label‐free mass spectrometry analysis. A non‐supervised statistical analysis (Posneg NMF) based on 352 differentially expressed proteins in both CTCL and psoriasis samples was able to separate the two disease groups and finally able to identify a set of 112 proteins that contributed most and significantly to the separation when compared to non‐lesional samples. In addition, Luminex assay revealed that the increase in the amount of chemokines related to the inflammatory response, and immune cell infiltration and recruitment in lesional stratum corneum in CTCL, including CXCL8, CXCL9, CXCL10, CCL27, TNF and sICAM‐1 was in agreement with published data on entire skin biopsies. Proteome analysis using quantitative methods including mass spectrometry and Luminex technology offered the possibility to investigate the relevant protein signature in CTCL and may be helpful to diagnose and investigate the efficacy of treatments in clinical investigations using non‐invasive methods in future.

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“…As a topical formulation, imiquimod has been demonstrated to have an antiviral effect and it has been approved by US Food and Drug Administration (FDA) for the treatment of external genital and perianal warts, superficial basal cell carcinoma, and actinic keratosis [7]. Furthermore, antiangiogenic [8] and proapoptotic effects on malignant keratinocytes, melanoma cells [9] [10], as well as T-lymphoma cells, both murine and human [11] have been demonstrated for this compound.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The use of imiquimod as an adjuvant in tumor vaccines may also contribute with additional benefits. Previous works carried out in our laboratory have demonstrated that this compound has an anti-proliferative effect in vitro on LBC cells through a dose-dependent induction of apoptosis, at concentrations between 1 and 100 µg/ml (Di Sciullo and Mongini personal communication) as it has been reported to have an oncolytic effect on other tumor cells [9] [10] [11]. Furthermore, imiquimod was also found to stimulate the proliferation of splenocytes at low doses, as was Imiquimod demonstrated to be a safe drug in this model when administered by the systemic route.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma

Sciullo

Menay

Cocozza

et al. 2019

Clinical Immunology

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Therapeutic Toll-like receptor agonists directly influence mouse and human T cell lymphoma cell viability and cytokine secretion

Cited by 3 publications

References 18 publications

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

Proteomic analysis of stratum corneum in Cutaneous T‐Cell Lymphomas and psoriasis

Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma

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