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Effect of naringin on gp120-induced injury mediated by P2X7 receptors in rat primary cultured microglia
Human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein 120 has been shown to activate microglia, causing release of inflammatory and toxic factors. The P2X7 receptor, primarily expressed on microglia, is closely associated with inflammation. Naringin, a plant bioflavonoid, has anti-inflam...
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Published in: | PloS one 2017-08, Vol.12 (8), p.e0183688 |
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description | Human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein 120 has been shown to activate microglia, causing release of inflammatory and toxic factors. The P2X7 receptor, primarily expressed on microglia, is closely associated with inflammation. Naringin, a plant bioflavonoid, has anti-inflammatory and anti-oxidative properties. We hypothesized that P2X7 receptor mediated gp120-induced injury in primary cultured microglia, and that naringin would have a protective effect. We showed that HIV-1 gp120 peptide (V3 loop, fragment 308-331) appeared to induce apoptosis of primary cultured microglia. However, there was a decrease of microglia apoptosis in gp120+naringin group compared with gp120 group. Using qPCR, Western blot, and immunofluorescence, we showed that gp120 stimulated expression of P2X7 mRNA and receptor protein, and this stimulation was inhibited by naringin. Treatment with gp120 increased concentrations of eATP, TNFα and IL-1β, and these effects were inhibited by naringin. Taken together, these results suggested that gp120 contributed to microglial cell injury and neurotoxic activity by up-regulating expression of P2X7, in a naringin-protective manner. |
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The P2X7 receptor, primarily expressed on microglia, is closely associated with inflammation. Naringin, a plant bioflavonoid, has anti-inflammatory and anti-oxidative properties. We hypothesized that P2X7 receptor mediated gp120-induced injury in primary cultured microglia, and that naringin would have a protective effect. We showed that HIV-1 gp120 peptide (V3 loop, fragment 308-331) appeared to induce apoptosis of primary cultured microglia. However, there was a decrease of microglia apoptosis in gp120+naringin group compared with gp120 group. Using qPCR, Western blot, and immunofluorescence, we showed that gp120 stimulated expression of P2X7 mRNA and receptor protein, and this stimulation was inhibited by naringin. Treatment with gp120 increased concentrations of eATP, TNFα and IL-1β, and these effects were inhibited by naringin. Taken together, these results suggested that gp120 contributed to microglial cell injury and neurotoxic activity by up-regulating expression of P2X7, in a naringin-protective manner.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0183688</identifier><identifier>PMID: 28832643</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adenosine Triphosphate - metabolism ; AIDS ; Animals ; Apoptosis ; Biology and Life Sciences ; Blotting, Western ; Cell injury ; Cells, Cultured ; Chemokines ; Cytokines ; Dementia ; Disease ; Flavanones - pharmacology ; Gene expression ; Glycoprotein gp120 ; Glycoproteins ; HIV ; HIV Envelope Protein gp120 - metabolism ; Human immunodeficiency virus ; Immunofluorescence ; In Situ Nick-End Labeling ; Infections ; Inflammation ; Injuries ; Interleukin 1 ; Interleukin-1beta - metabolism ; Kinases ; Laboratory animals ; Medicine and Health Sciences ; Microglia ; Microglia - drug effects ; Microglia - metabolism ; mRNA ; Neurotoxicity ; Pathogenesis ; Physiology ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptors ; Receptors, Purinergic P2X7 - genetics ; Receptors, Purinergic P2X7 - metabolism ; Research and Analysis Methods ; RNA, Messenger - genetics ; Rodents ; Stimulation ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-TNF ; Viruses</subject><ispartof>PloS one, 2017-08, Vol.12 (8), p.e0183688</ispartof><rights>2017 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The P2X7 receptor, primarily expressed on microglia, is closely associated with inflammation. Naringin, a plant bioflavonoid, has anti-inflammatory and anti-oxidative properties. We hypothesized that P2X7 receptor mediated gp120-induced injury in primary cultured microglia, and that naringin would have a protective effect. We showed that HIV-1 gp120 peptide (V3 loop, fragment 308-331) appeared to induce apoptosis of primary cultured microglia. However, there was a decrease of microglia apoptosis in gp120+naringin group compared with gp120 group. Using qPCR, Western blot, and immunofluorescence, we showed that gp120 stimulated expression of P2X7 mRNA and receptor protein, and this stimulation was inhibited by naringin. Treatment with gp120 increased concentrations of eATP, TNFα and IL-1β, and these effects were inhibited by naringin. Taken together, these results suggested that gp120 contributed to microglial cell injury and neurotoxic activity by up-regulating expression of P2X7, in a naringin-protective manner.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>AIDS</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Blotting, Western</subject><subject>Cell injury</subject><subject>Cells, Cultured</subject><subject>Chemokines</subject><subject>Cytokines</subject><subject>Dementia</subject><subject>Disease</subject><subject>Flavanones - pharmacology</subject><subject>Gene expression</subject><subject>Glycoprotein gp120</subject><subject>Glycoproteins</subject><subject>HIV</subject><subject>HIV Envelope Protein gp120 - metabolism</subject><subject>Human immunodeficiency virus</subject><subject>Immunofluorescence</subject><subject>In Situ Nick-End Labeling</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Injuries</subject><subject>Interleukin 1</subject><subject>Interleukin-1beta - 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The P2X7 receptor, primarily expressed on microglia, is closely associated with inflammation. Naringin, a plant bioflavonoid, has anti-inflammatory and anti-oxidative properties. We hypothesized that P2X7 receptor mediated gp120-induced injury in primary cultured microglia, and that naringin would have a protective effect. We showed that HIV-1 gp120 peptide (V3 loop, fragment 308-331) appeared to induce apoptosis of primary cultured microglia. However, there was a decrease of microglia apoptosis in gp120+naringin group compared with gp120 group. Using qPCR, Western blot, and immunofluorescence, we showed that gp120 stimulated expression of P2X7 mRNA and receptor protein, and this stimulation was inhibited by naringin. Treatment with gp120 increased concentrations of eATP, TNFα and IL-1β, and these effects were inhibited by naringin. Taken together, these results suggested that gp120 contributed to microglial cell injury and neurotoxic activity by up-regulating expression of P2X7, in a naringin-protective manner.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28832643</pmid><doi>10.1371/journal.pone.0183688</doi><orcidid>https://orcid.org/0000-0002-3928-3605</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acquired immune deficiency syndrome Adenosine Triphosphate - metabolism AIDS Animals Apoptosis Biology and Life Sciences Blotting, Western Cell injury Cells, Cultured Chemokines Cytokines Dementia Disease Flavanones - pharmacology Gene expression Glycoprotein gp120 Glycoproteins HIV HIV Envelope Protein gp120 - metabolism Human immunodeficiency virus Immunofluorescence In Situ Nick-End Labeling Infections Inflammation Injuries Interleukin 1 Interleukin-1beta - metabolism Kinases Laboratory animals Medicine and Health Sciences Microglia Microglia - drug effects Microglia - metabolism mRNA Neurotoxicity Pathogenesis Physiology Rats Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Receptors Receptors, Purinergic P2X7 - genetics Receptors, Purinergic P2X7 - metabolism Research and Analysis Methods RNA, Messenger - genetics Rodents Stimulation Tumor necrosis factor Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-TNF Viruses |
title | Effect of naringin on gp120-induced injury mediated by P2X7 receptors in rat primary cultured microglia |
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