Alpha-Melanocyte Stimulating Hormone (α-MSH) Is a Post-Caspase Suppressor of Apoptosis in RAW 264.7 Macrophages

Taylor, Andrew W.

doi:10.1371/journal.pone.0074488

Cited by 14 publications

(15 citation statements)

References 30 publications

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“…It was also demonstrated that mouse RPE cells could activate macrophages to function similar to myeloid suppressor cells. This effect was mediated by alpha-melanocyte-stimulating hormone as an immunosuppressive regulator ( Taylor, 2013 ). Similarly, the mechanism of immunomodulaton by hESC-RPE cells may be complex and may involve regulation of various immune cells.…”

Section: Discussionmentioning

confidence: 99%

Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

et al. 2018

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SummaryAge-related macular degeneration is caused by dysfunction and loss of retinal pigment epithelium (RPE) cells, and their transplantation may rescue visual functions and delay disease progression. Human embryonic stem cells (hESCs) may be an unlimited source of RPE cells for allotransplantation. We analyzed the immunomodulatory properties of hESC-derived RPE (hESC-RPE) cells, and showed that they inhibited T cell responses. Co-culture experiments showed that RPE cells inhibited interfon-γ secretion and proliferation of activated T cells. Furthermore, hESC-RPE cells enhanced T cell apoptosis and secretion of the anti-inflammatory cytokine interleukin-10 (IL-10). In addition, RPE cells altered the expression of T cell activation markers, CD69 and CD25. RPE cells transplanted into RCS rats without immunosuppression survived, provided retinal rescue, and enhanced IL-10 blood levels. Our data suggest that hESC-RPE cells have immunosuppressive properties. Further studies will determine if these properties are sufficient to alleviate the need for immunosuppression therapy after their clinical allotransplantation.

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Section: Discussionmentioning

confidence: 99%

Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

et al. 2018

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“…This has suggested that the RPE produce a pro-apoptotic signal in macrophages that is countered by α-MSH. The apoptotic signal blocked by α-MSH, or how α-MSH blocks apoptosis is not yet understood [20]. In parallel, the ARPE-19 conditioned media depleted of α-MSH and NPY were significantly diminished in their capacity to suppress activation of the phagolysosome in macrophages, and the macrophages treated with the depleted conditioned media are appearing to be dying.…”

Section: Discussionmentioning

confidence: 99%

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Taylor

Dixit

2015

IJOES

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The eye is an immune privileged tissue with multiple mechanisms of immunosuppression to protect the light gathering tissues from the damage of inflammation. One of theses mechanisms involves retinal pigment epithelial cell suppression of phagosome activation in macrophages. The objective of this work is to determine if the human RPE cell line ARPE-19 is capable of suppressing the activation of the phagolysosome in macrophages in a manner similar to primary RPE. The conditioned media of RPE eyecups, sub-confluent, just confluent cultures, or established confluent cultures of human ARPE-19 cells were generated. These condition media were used to treat macrophages phagocytizing pHrodo bioparticles. After 24 hours incubation the macrophages were imaged by fluorescent microscopy, and fluorescence was measured. The fluorescent intensity is proportional to the amount of bioparticles phagocytized and are in an activated phagolysosome. The conditioned media of in situ mouse RPE eyecups significantly suppressed the activation of phagolysosome. The conditioned media from cultures of human ARPE-19 cells, grown to sub-confluence (50%) or grown to confluence had no effect on phagolysosome activation. In contrast, the conditioned media from established confluent cultures significantly suppressed phagolysosome activation. The neuropeptides alpha-MSH and NPY were depleted from the conditioned media of established confluent ARPE-19 cell cultures. This depleted conditioned media had diminished suppression of phagolysosome activation while promoting macrophage cell death. In addition, the condition media from cultures of ARPE-19 monolayers wounded with a bisecting scrape was diminished in suppressing phagolysosome activation. This technical report suggests that like primary RPE monolayers, established confluent cultures of ARPE-19 cells produce soluble factors that suppress the activation of macrophages, and can be used to study the molecular mechanisms of retinal immunobiology. In addition, the results further demonstrate the importance of an intact monolayer of RPE cells to modulate immune cell activity within the eye.

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“…In murine primary macrophages, the MCR agonist AP124 promotes phagocytosis of zymosan particles and of apoptotic neutrophils acting mainly through MC3R [78]. However, treatment of RAW 264.7 cells with α -MSH reduces phagocytosis of apoptotic cells [79] and E. coli bioparticles, and when combined with NPY it also reduces phagocytosis of gram-positive bioparticles [80]. Our group found that treatment of primary rat microglia with NDP-MSH does not affect basal or LPS-induced phagocytosis of latex beads; however, NDP-MSH inhibits phagocytosis induced by the TLR2 agonist Pam 3 CSK 4 in microglial cells [49].…”

Section: Pomc-derived Peptidesmentioning

confidence: 99%

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Carniglia

Ramírez

Durand

et al. 2017

Mediators of Inflammation

183

129

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Microglial cells are responsible for immune surveillance within the CNS. They respond to noxious stimuli by releasing inflammatory mediators and mounting an effective inflammatory response. This is followed by release of anti-inflammatory mediators and resolution of the inflammatory response. Alterations to this delicate process may lead to tissue damage, neuroinflammation, and neurodegeneration. Chronic pain, such as inflammatory or neuropathic pain, is accompanied by neuroimmune activation, and the role of glial cells in the initiation and maintenance of chronic pain has been the subject of increasing research over the last two decades. Neuropeptides are small amino acidic molecules with the ability to regulate neuronal activity and thereby affect various functions such as thermoregulation, reproductive behavior, food and water intake, and circadian rhythms. Neuropeptides can also affect inflammatory responses and pain sensitivity by modulating the activity of glial cells. The last decade has witnessed growing interest in the study of microglial activation and its modulation by neuropeptides in the hope of developing new therapeutics for treating neurodegenerative diseases and chronic pain. This review summarizes the current literature on the way in which several neuropeptides modulate microglial activity and response to tissue damage and how this modulation may affect pain sensitivity.

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Alpha-Melanocyte Stimulating Hormone (α-MSH) Is a Post-Caspase Suppressor of Apoptosis in RAW 264.7 Macrophages

Cited by 14 publications

References 30 publications

Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

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