HSP70 Modulates the Enhanced Production of Reactive Intermediate Metabolites and a Proinflammatory Cytokine TNF-α Expression in a T Cell Lymphoma

Kumar, Sanjay; Deepak, Praveen; Acharya, Arbind

doi:10.1177/1721727x0600400304

Cited by 6 publications

(1 citation statement)

References 30 publications

(28 reference statements)

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“…However, in the previous studies of HSP70, the dose was generally HSP70 266 ug/KgBB/ip to suggest, exogenous HSP70 dose of 266 μg/kgBW in mice increases the number of BCL 2 which can inhibit apoptosis [18]. In his study, Kumar et al used HSP70 injection tumor models, dosages varied from 1 µg to 100 µg to improve TNF-α production [24]. As Choudhoury et al (2011) states, exogenous HSP70 administration inhibits apoptosis through the prevention of Cyt c complex release pathways, apoptotic proteaseactivating factor 1 (apaf 1), pro-Caspase 9 and 3.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of 200 Μg/KGBW/Ip Heat Shock Protein-70 in Reduction of Cyt C, Bax, and Caspase 3 Expression, and Mortality in Mice Model With Multiple Organ Dysfunction Syndrome

Sukamto

Suroto

Mudigdo

et al. 2018

Asian J Pharm Clin Res

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Objective: Heat shock protein 70 (HSP70) decreases Cyt expression c, Bax, and Caspase 3 in apoptosis multiple organ dysfunction syndrome (MODS), thus inhibiting death. This study aimed to analyze the efficacy of HSP70 200 μg/KgBB/ip to decrease Cyt c, Bax, and Caspase 3 expression, to reduce mortality, and to increase survival rate, in the MOD alveolar lung epithelial of 78-h sepsis model.Methods: This was a post-test only quasi-experiment conducted at Inter-University Central Laboratory of Gadjah Mada University, Yogyakarta, and the Anatomy Pathology Laboratory, Faculty of Medicine, Universitas Sebelas Maret, Surakarta. The study used a type of Balb/c mice, male, aged of 6–8 weeks, body weight of 25–33 g. Sepsis induction used LIG SIGMA L2880-10MG Lot #025M4040V from Escherichia coli 055:B5 purified by phenol extraction. Medication to reduce mortality used HSP70 Lot #L16020515 and then continued with 400× immunohistochemistry (IHC) examination. A sample of 30 mice were divided into three groups: (1) Control group without 78 h treatment, (2) lipopolysaccharide (LPS) group with a dose of 0.25 mg/kgBW/ip 78 h, and (3) HSP70 group with a dose of 200 μg/kgBB/ip after LPS injection 0.25 mg/kgBW/ip 78 h. The outcome variables included expression of Cyt, Bax, Caspase 3, and mortality in mice model with multiple organ dysfunction syndrome. The data were analyzed by Kruskal–Wallis and continued by Mann–Whitney U-test. Results: Administration of HSP70 200 mg/KgBW/ip after LPS 0.25 mg/kgBW/ip significantly decreased Cyt c expression (p=0.014), Bax (p=0.004), and Caspase 3 (p=0.015) in 78 h pulmonary alveolar cells, reduced mortality rate, and increased the number of survivors. Expressions of Cyt c, Bax, and Caspase 3 of IHC 400× magnification had a near-normal image change.Conclusion: There is a decrease of Cyt c, Bax, and Caspase 3 expression in the MOD alveolar lung epithelial cells of the 78-h sepsis model mice, a decrease of mortality rate, and an increase of survival rate, and the image of IHC is almost normal.

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Section: Discussionmentioning

confidence: 99%

The Efficacy of 200 Μg/KGBW/Ip Heat Shock Protein-70 in Reduction of Cyt C, Bax, and Caspase 3 Expression, and Mortality in Mice Model With Multiple Organ Dysfunction Syndrome

Sukamto

Suroto

Mudigdo

et al. 2018

Asian J Pharm Clin Res

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CD28-mediated T cell response is upregulated by exogenous application of autologous Hsp70–peptide complex in a tumor-bearing host

et al. 2015

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Hsp70, a highly conserved protein, has gained plenty of attention by virtue of its adjuvant capability to induce peptide-specific cytotoxic T lymphocyte responses. In this study, we have investigated the effect of autologous Hsp70-peptide complex (or simply autologous Hsp70) on the expression of CD28 on T cells and its effector functions through macrophage activation. Further, we investigated the effect of Hsp70 on the expression of CD80 and CD86 on macrophages isolated from normal and tumor-bearing host to provide costimulatory signal for T cell activation and secretion of IL-2 and IFN-γ during interaction. We found that treatment of autologous Hsp70 effectively activated TAMs to induce higher expression of CD28 on T cells through T cells-macrophage interaction. Treatment of autologous Hsp70 induces higher expression of CD80 and CD86 on TAMs, as a result, increases B7/CD28 interaction, which in turns activates T cells and induces higher production of IL-2 and IFN-γ, thereby increasing antigen-specific T cell proliferation. With our novel study, we have provided the strong insights into the role of extracellular Hsp70 on the expression of CD28 costimulatory molecule on T cells, which helps in the activation and generation of antigen-specific T cell effector functions in a tumor-bearing host to curb malignancy.

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Morphological effects of autologous hsp70 on peritoneal macrophages in a murine T cell lymphoma

et al. 2013

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Heat shock protein 70 is highly conserved cytosolic protein which have important role in growth, development, and apoptosis. Hsp70 is well-known activator of macrophages and enhances the release of specific and non-specific effector molecules that have major role in tumor destruction and immunopotentiation of host. However, morphological effects of hsp 70 has not been carried out, therefore, morphological effects of hsp 70 on murine peritoneal macrophages were examined by light microscopy and scanning electron microscopy. Thioglycolate-induced peritoneal macrophages were prepared from BALB/c mice and cultured for 24 h in the presence of the hsp70. Tumor-associated macrophages treated with 10 μg/ml were varied in shape, mostly spindle shaped, i.e., stretched bidirectionally; surface ruffles were increased and their lamellipodia was prominent which suggest that hsp 70 treatment not only enhances the functional state of the peritoneal macrophages but also initiate immense morphological changes leading to increased endothelium adherence, increased antigen uptake, and increased migration to the inflammatory site.

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HSP70 Modulates the Enhanced Production of Reactive Intermediate Metabolites and a Proinflammatory Cytokine TNF-α Expression in a T Cell Lymphoma

Cited by 6 publications

References 30 publications

The Efficacy of 200 Μg/KGBW/Ip Heat Shock Protein-70 in Reduction of Cyt C, Bax, and Caspase 3 Expression, and Mortality in Mice Model With Multiple Organ Dysfunction Syndrome

The Efficacy of 200 Μg/KGBW/Ip Heat Shock Protein-70 in Reduction of Cyt C, Bax, and Caspase 3 Expression, and Mortality in Mice Model With Multiple Organ Dysfunction Syndrome

CD28-mediated T cell response is upregulated by exogenous application of autologous Hsp70–peptide complex in a tumor-bearing host

Morphological effects of autologous hsp70 on peritoneal macrophages in a murine T cell lymphoma

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