The Role of Recombinant Human Cyclophilin A in the Antitumor Immune Response

Cyclophilin A (CypA) is a multifunctional protein that exhibits an isomerase activity and exists in the intracellular and secretory forms. Secretory CypA promotes regeneration of the hematopoietic and the immune systems of an organism by stimulating stem cell migration from the bone marrow. New approaches based on CypA are currently being developed for the treatment of limb ischemia, neutralization of the side effects of Cyclosporine A (CsA) therapy, etc. However, the role of CypA in the antitumor immune response is still unexplored. In this work, we used the model experimental system of lymphoma EL-4 rejection in B10.D2(R101) mice and showed that recombinant human CypA (rhCypA) stimulates the antitumor immune response via early recruitment of granulocytes to the tumor cell localization site and rapid accumulation of effector T-killers

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Faculty Opinions recommendation of Critical role of cyclophilin A and its prolyl-peptidyl isomerase activity in the structure and function of the hepatitis C virus replication complex.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1162955.623591 ◽

2009 ◽

Author(s):

Teresa Compton

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Replication ◽

Critical Role ◽

Cyclophilin A ◽

Structure And Function ◽

Replication Complex ◽

Isomerase Activity ◽

And Function

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Abstract 2676: Role of the RON kinase in the regulation of the antitumor immune response in pancreatic cancer

10.1158/1538-7445.am2017-2676 ◽

2017 ◽

Author(s):

Alex Cazes ◽

Michele L. Babicky ◽

Jeffery Chakedis ◽

Divya Sood ◽

Dawn Jaquish ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Response ◽

Antitumor Immune Response

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Role of Gene Methylation in Antitumor Immune Response: Implication for Tumor Progression

Cancers ◽

10.3390/cancers3021672 ◽

2011 ◽

Vol 3 (2) ◽

pp. 1672-1690 ◽

Cited By ~ 14

Author(s):

Alfonso Serrano ◽

Isabel Castro-Vega ◽

Maximino Redondo

Keyword(s):

Immune Response ◽

Tumor Progression ◽

Antitumor Immune Response ◽

Gene Methylation

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Evidence that cyclophilin-A protects cells against oxidative stress

Biochemical Journal ◽

10.1042/bj3410127 ◽

1999 ◽

Vol 341 (1) ◽

pp. 127-132 ◽

Cited By ~ 44

Author(s):

Veronica DOYLE ◽

Sukaina VIRJI ◽

Martin CROMPTON

Keyword(s):

Cell Death ◽

Cyclosporin A ◽

Cyclophilin A ◽

Cell Extract ◽

Protective Role ◽

Cyclophilin D ◽

Isomerase Activity ◽

Neonatal Cardiomyocytes ◽

Sds Page

Cyclophilin-A is the cytosolic isoform of a family of peptidylproline cis-trans-isomerases that bind cyclosporin A. This study investigates the role of cyclophilin-A in necrotic cell death, induced by ‘chemical ischaemia’ and by t-butylhydroperoxide. An 18-mer antisense phosphorothioate oligodeoxynucleotide was used to target a translated region of cyclophilin-A mRNA in rat neonatal cardiomyocytes. After a 24 h exposure to the oligonucleotide, the amount of cyclophilin-A in the cells was decreased by at least 93% as judged by immunological and enzymic criteria. For the enzyme assays, peptidyl proline cis-trans-isomerase activity was measured fluorimetrically in small (10 μl) volumes of cell extract. Immunoblots were developed with a polyclonal anti-cyclophilin-A antibody after sample isoelectric focusing and SDS/PAGE. Cyclophilin-A suppression had no effect on cyanide-plus-2-deoxyglucose-induced cell death. However, cyclophilin-A-suppressed cells were markedly more sensitive to t-butylhydroperoxide. Cyclosporin A conferred some resistance to the peroxide in both types of cell, but protection was greater in cyclophilin-A-suppressed cells, where cyclosporin A increased the survival time 2-fold. It is concluded that two cyclophilin isoforms are involved, in quite different ways, in peroxide-induced cell death. Cyclophilin-A has a protective role. Another isoform, possibly mitochondrial cyclophilin-D, has a deleterious role, such that blockade by cyclosporin A leads to protection.

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Lipophilicity of Bacteriochlorin-Based Photosensitizers as a Determinant for PDT Optimization through the Modulation of the Inflammatory Mediators

Journal of Clinical Medicine ◽

10.3390/jcm9010008 ◽

2019 ◽

Vol 9 (1) ◽

pp. 8 ◽

Cited By ~ 8

Author(s):

Barbara Pucelik ◽

Luis G. Arnaut ◽

Janusz M. Dąbrowski

Keyword(s):

Immune Response ◽

Molecular Mechanisms ◽

Near Infrared ◽

Antitumor Immune Response ◽

Infrared Light ◽

Gm Csf ◽

Hydrophobic Compound ◽

Tnf Α ◽

Wide Range

Photodynamic therapy (PDT) augments the host antitumor immune response, but the role of the PDT effect on the tumor microenvironment in dependence on the type of photosensitizer and/or therapeutic protocols has not been clearly elucidated. We employed three bacteriochlorins (F2BOH, F2BMet and Cl2BHep) of different polarity that absorb near-infrared light (NIR) and generated a large amount of reactive oxygen species (ROS) to compare the PDT efficacy after various drug-to-light intervals: 15 min. (V-PDT), 3h (E-PDT) and 72h (C-PDT). We also performed the analysis of the molecular mechanisms of PDT crucial for the generation of the long-lasting antitumor immune response. PDT-induced damage affected the integrity of the host tissue and developed acute (protocol-dependent) local inflammation, which in turn led to the infiltration of neutrophils and macrophages. In order to further confirm this hypothesis, a number of proteins in the plasma of PDT-treated mice were identified. Among a wide range of cytokines (IL-6, IL-10, IL-13, IL-15, TNF-α, GM-CSF), chemokines (KC, MCP-1, MIP1α, MIP1β, MIP2) and growth factors (VEGF) released after PDT, an important role was assigned to IL-6. PDT protocols optimized for studied bacteriochlorins led to a significant increase in the survival rate of BALB/c mice bearing CT26 tumors, but each photosensitizer (PS) was more or less potent, depending on the applied DLI (15 min, 3 h or 72 h). Hydrophilic (F2BOH) and amphiphilic (F2BMet) PSs were equally effective in V-PDT (>80 cure rate). F2BMet was the most efficient in E-PDT (DLI = 3h), leading to a cure of 65 % of the animals. Finally, the most powerful PS in the C-PDT (DLI = 72 h) regimen turned out to be the most hydrophobic compound (Cl2BHep), allowing 100 % of treated animals to be cured at a light dose of only 45 J/cm2.

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