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Project description:Bryostatin-1, a pharmacological agent from marine organisms, has been studied for HIV and cancer therapies due to its modulation of protein kinase C. In our previous study (Zhao M et al. Pharmacological research. 2019;139:524-34.), we found that bryostatin-1 downregulated inhibitory receptor PD-1 on activated CD8+ T cells from people with HIV. Since HIV-specific CD8+ T cells become functionally exhausted during chronic HIV infection and PD-1 expression is known to be related to the exhaustion state of these cells, we hypothesized that bryostatin-1 may modulate CD8+ T cell exhaustion. To test this, we generated in vitro exhausted OT-I CD8+ T cells as previously described (Zhao M et al PLoS Pathog. 16(6): e1008555) by repeatedly stimulating cells with OVA(257-264) peptide. Then we treated both exhausted CD8+ T cells (repeat peptide stimulated cells) and non-exhausted CD8+ T cells (single peptide stimulated cells) with bryostatin-1 for 3 days. We found that bryostatin-1 decreased exhaustion-associated markers and improved the functionality of exhausted CD8+ T cells. To investigate the underlying mechanism of how bryostatin-1 exerts its effects on exhausted CD8+ T cells, we performed RNA-sequencing (RNA-seq) on in vitro exhausted OT- I CD8+ T cells which were treated with bryostatin-1 or DMSO, with single peptide stimulated cells as non-exhausted controls. Taken together, our study demonstrate bryostatin-1's effect on exhausted CD8+ T cells and bryostatin-1's potential in enhancing T cell immunity against chronic infection or cancer.
2025-01-06 | GSE284406 | GEO
Project description:To investigate bryostain's effect on Raji , we performed a whole-transcriptome RNA sequencing experiment for Raji cells treated with Bryostatin and established differntial expression profile comparing to raji treated with DMSO.
2022-08-19 | GSE211351 | GEO
Project description:Effect of the Bryostatin 1 in B cells
| PRJNA1139742 | ENA
Project description:Effect of bryostatin-1 on in vitro exhausted CD8+ T cells
| PRJNA1198962 | ENA
Project description:Effect of bryostatin-1 on gene expression profile of Raji cells
| PRJNA869939 | ENA
Project description:Bryostatin 1, like the phorbol ester PMA, activates protein kinase C (PKC) in vitro but paradoxically blocks many phorbol ester responses in vivo. Results with a limited panel of genes suggested that transiency of action was an important mechanism contributing to this differential cellular response. Here, we examined global gene expression in LNCaP and U937 cell lines to probe the extent to which transiency of action captures the difference in response. While different genes showed different patterns of relative response, the overall pattern was reflective of an initial PMA-like response to bryostatin 1 followed by variable transiency of the continued response. This conclusion was further strengthened by detailed time course measurements by qPCR of selected genes. Merle 23, a bryostatin derivative with biological behavior intermediate between that of bryostatin 1 and PMA, was likewise intermediate for transiency of action. Both the LNCaP and U937 cell lines behaved similarly, but the extent of transiency in response to bryostatin 1 was greater in the LNCaP cells.
2017-12-30 | GSE104374 | GEO
Project description:Bryostatin 1, like the phorbol ester PMA, activates protein kinase C (PKC) in vitro but paradoxically blocks many phorbol ester responses in vivo. Results with a limited panel of genes suggested that transiency of action was an important mechanism contributing to this differential cellular response. Here, we examined global gene expression in LNCaP and U937 cell lines to probe the extent to which transiency of action captures the difference in response. While different genes showed different patterns of relative response, the overall pattern was reflective of an initial PMA-like response to bryostatin 1 followed by variable transiency of the continued response. This conclusion was further strengthened by detailed time course measurements by qPCR of selected genes. Merle 23, a bryostatin derivative with biological behavior intermediate between that of bryostatin 1 and PMA, was likewise intermediate for transiency of action. Both the LNCaP and U937 cell lines behaved similarly, but the extent of transiency in response to bryostatin 1 was greater in the LNCaP cells.
2017-12-30 | GSE104373 | GEO
Project description:In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining the balance between myelin repair and demyelination/neurodegeneration. Phagocytic and regenerative functions of these CNS innate immune cells support remyelination, whereas chronic and maladaptive inflammatory activation promotes lesion expansion and disability, particularly in the progressive forms of MS. No currently approved drugs convincingly target microglia and macrophages within the CNS, contributing to the critical lack of therapies promoting remyelination and slowing progression in MS. Here, we found that the protein kinase C (PKC)-modulating drug bryostatin-1 (bryo-1), a CNS-penetrant compound with an established human safety profile, produces a shift in microglia and CNS macrophage transcriptional programs from pro-inflammatory to regenerative phenotypes, both in vitro and in vivo. Treatment of microglia with bryo-1 stimulated scavenger pathways, phagocytosis, and secretion of factors that prevent the activation of neuroinflammatory reactive astrocytes while promoting neuroaxonal health and oligodendrocyte differentiation. In line with these findings, systemic treatment with bryo-1 augmented remyelination following a focal demyelinating injury in vivo. Our results demonstrate the potential of bryo-1 and possibly a wider class of PKC modulators as myelin regenerative and supportive agents in MS and other neurologic diseases through therapeutic targeting of microglia and CNS-associated macrophages.
2024-10-29 | GSE280579 | GEO
Project description:In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining the balance between myelin repair and demyelination/neurodegeneration. Phagocytic and regenerative functions of these CNS innate immune cells support remyelination, whereas chronic and maladaptive inflammatory activation promotes lesion expansion and disability, particularly in the progressive forms of MS. No currently approved drugs convincingly target microglia and macrophages within the CNS, contributing to the critical lack of therapies promoting remyelination and slowing progression in MS. Here, we found that the protein kinase C (PKC)-modulating drug bryostatin-1 (bryo-1), a CNS-penetrant compound with an established human safety profile, produces a shift in microglia and CNS macrophage transcriptional programs from pro-inflammatory to regenerative phenotypes, both in vitro and in vivo. Treatment of microglia with bryo-1 stimulated scavenger pathways, phagocytosis, and secretion of factors that prevent the activation of neuroinflammatory reactive astrocytes while promoting neuroaxonal health and oligodendrocyte differentiation. In line with these findings, systemic treatment with bryo-1 augmented remyelination following a focal demyelinating injury in vivo. Our results demonstrate the potential of bryo-1 and possibly a wider class of PKC modulators as myelin regenerative and supportive agents in MS and other neurologic diseases through therapeutic targeting of microglia and CNS-associated macrophages.
2024-10-29 | GSE280578 | GEO
Project description:RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of bryostatin 1 in treating patients with metastatic colorectal cancer.
| 2002785 | ecrin-mdr-crc