TY  - JOUR
A1  - Nadella, Vinod
A1  - Mohanty, Aparna
A1  - Sharma, Lalita
A1  - Yellaboina, Sailu
A1  - Mollenkopf, Hans-Joachim
A1  - Mazumdar, Varadendra Balaji
A1  - Palaparthi, Ramesh
A1  - Mylavarapu, Madhavi B.
A1  - Maurya, Radheshyam
A1  - Kurukuti, Sreenivasulu
A1  - Rudel, Thomas
A1  - Prakash, Hridayesh
T1  - Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory Responses
JF  - Frontiers in Immunology
N2  - Apoptosis is a physiological cell death process essential for development, tissue homeostasis, and for immune defense of multicellular animals. Inhibitors of apoptosis proteins (IAPs) regulate apoptosis in response to various cellular assaults. Using both genetic and pharmacological approaches we demonstrate here that the IAPs not only support opportunistic survival of intracellular human pathogens like Chlamydia pneumoniae but also control plasticity of iNOS+ M1 macrophage during the course of infection and render them refractory for immune stimulation. Treatment of Th1 primed macrophages with birinapant (IAP-specific antagonist) inhibited NO generation and relevant proteins involved in innate immune signaling. Accordingly, birinapant promoted hypoxia, angiogenesis, and tumor-induced M2 polarization of iNOS+ M1 macrophages. Interestingly, birinapant-driven changes in immune signaling were accompanied with changes in the expression of various proteins involved in the metabolism, and thus revealing the new role of IAPs in immune metabolic reprogramming in committed macrophages. Taken together, our study reveals the significance of IAP targeting approaches (Smac mimetic compounds) for the management of infectious and inflammatory diseases relying on macrophage plasticity.
KW  - apoptosis
KW  - macrophages immunobiology
KW  - inflammation mediators
KW  - polarization
KW  - infection
KW  - hypothalamus
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197484
SN  - 1664-3224
VL  - 8
IS  - 1792
ER  - 
TY  - JOUR
A1  - Grebinyk, Anna
A1  - Grebinyk, Sergii
A1  - Prylutska, Svitlana
A1  - Ritter, Uwe
A1  - Matyshevska, Olga
A1  - Dandekar, Thomas
A1  - Frohme, Marcus
T1  - C60 fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy
JF  - Free Radical Biology and Medicine
N2  - Recent progress in nanobiotechnology has attracted interest to a biomedical application of the carbon nanostructure C60 fullerene since it possesses a unique structure and versatile biological activity. C60 fullerene potential application in the frame of cancer photodynamic therapy (PDT) relies on rapid development of new light sources as well as on better understanding of the fullerene interaction with cells.

The aim of this study was to analyze C60 fullerene effects on human leukemic cells (CCRF-CEM) in combination with high power single chip light-emitting diodes (LEDs) light irradiation of different wavelengths: ultraviolet (UV, 365 nm), violet (405 nm), green (515 nm) and red (632 nm). The time-dependent accumulation of fullerene C60 in CCRF-CEM cells up to 250 ng/106 cells at 24 h with predominant localization within mitochondria was demonstrated with immunocytochemical staining and liquid chromatography mass spectrometry. In a cell viability assay we studied photoexcitation of the accumulated C60 nanostructures with ultraviolet or violet LEDs and could prove that significant phototoxic effects did arise. A less pronounced C60 fullerene phototoxic effect was observed after irradiation with green, and no effect was detected with red light. A C60 fullerene photoactivation with violet light induced substantial ROS generation and apoptotic cell death, confirmed by caspase3/7 activation and plasma membrane phosphatidylserine externalization. Our work proved C60 fullerene ability to induce apoptosis of leukemic cells after photoexcitation with high power single chip 405 nm LED as a light source. This underlined the potential for application of C60 nanostructure as a photosensitizer for anticancer therapy.
KW  - C-60 fullerene
KW  - photodanamic therapy
KW  - LEDs
KW  - leukemic cells
KW  - immunocytochemistry
KW  - HPLC-ESI-MS
KW  - apoptosis
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228245
VL  - 124
ER  -