[PubMed] [Google Scholar]Lehmann MH, Masanetz S, Kramer S, Erfle V

[PubMed] [Google Scholar]Lehmann MH, Masanetz S, Kramer S, Erfle V. CCR5 and CXCR4, which serve as gp120 co-receptors, were detected in progenitors. We postulate that chemokine production by progenitors may be a normal, adaptive process that encourages immune inspection of newly generated cells. Pathogens such as HIV might usurp this function to create a maladaptive state, especially during development or regeneration, when progenitors are numerous. 2003, Torres-Munoz 2001). Neuropathology is instead mediated by direct neurotoxic actions of released viral proteins, or secondarily, through toxic effects orchestrated by glial cells (Kaul 2001, Gendelman 1994, Persidsky & Gendelman 2003, Hauser 2007, Brack-Werner 1999, Kramer-Hammerle 2005b). HIV-infected macrophages/microglia reaching the brain create a reservoir of viral infection, and lay the groundwork for inflammation leading to neuropathology and cognitive changes. Although there is little evidence that macroglial cells in vivo are productively infected by HIV (Kramer-Hammerle et al. 2005b, Brack-Werner 1999, Gorry 2003), activation of astroglia by viral proteins, or by substances released from reactive microglia, can amplify brain inflammation and neurotoxic sequelae, and also promote infiltration of infected monocytes from the periphery. Thus, HIV neuropathology results from collective effects of viral proteins and inflammatory mediators on several cell types. Astroglia from humans and rodents secrete chemokine/cytokines in response to HIV-1 transactivator of transcription (Tat) protein (Nath 1999, El-Hage 2005, Kutsch 2000, McManus 2000, Rappaport 1999, Conant 1998). We have shown that Tat-induced [Ca2+]i responses mediate CCL2/MCP-1, CCL5/RANTES and interleukin-6 (IL-6) release, resulting in downstream signaling through NFB-dependent pathways (El-Hage et al. 2005, El-Hage 2008b). Concurrent exposure to morphine exacerbates Tat-induced chemokine/cytokine production and microglial activation through CCL5/RANTES-driven amplification of CCL2/MCP-1 (El-Hage 2008a, El-Hage 2006a, El-Hage 2006b, Bruce-Keller 2008), an observation that may partly explain relatively high incidences of microglial activation, neuropathology and cognitive disturbance among HIV patients who abuse opiates (Bell 2006, Arango 2004, Anthony 2008, Bouwman 1998, Dougherty 2002). Astroglia are also sensitive to gp120, which can elevate [Ca2+]i (Codazzi 1996, Holden 1999), and alter gene expression (Wang 2004, Galey 2003) leading to chemokine/cytokine secretion (Buriani 1999, Kong 1996, Ronaldson & Bendayan 2006, Yeung 1995), with some evidence for exacerbation by opioids (Mahajan 2005). In our hands, Tat generally elicits more chemokine/cytokine secretion than gp120, and the responsivity varies with brain regional (Fitting 2010). Responses of astroglia to other HIV-1 proteins have been less well studied (Kramer-Hammerle 2005a, Lehmann 2006). We were intrigued by the possibility that less differentiated CNS cells, in addition to microglia and astroglia, might secrete inflammatory mediators. This would parallel situations in other tissues. Unstimulated bone marrow or cord-derived mesenchymal stem cells secrete a spectrum of chemokine/cytokines and growth factors, including multiple FGFs, interleukins, IGF-1, leukemia inhibitory factor, CCL2/MCP-1, MIP-1, MIP-1, SDF-1, and VEGF (Rafei 2008, Croitoru-Lamoury 2007, Schinkothe 2008, Chen 2008, Liu & Hwang 2005, Wagner 2007). As mesenchymal stem cells differentiate, the balance of factors released varies with cell fate (Molloy 2009, Kilroy 2007). Neural progenitor cells (NPCs), which derive from undifferentiated neuroepithelial cells, are a self-renewing and multipotential source of neurons and macroglial cells. Common markers for NPCs include the intermediate filament nestin and the transcription chroman 1 factor Sox2 (sex determining region of Y (SRY)-related HMG-box gene 2). As NPCs differentiate, they become largely restricted to either neuronal or glial fates. Differentiating glial-restricted progenitors (GPCs) express markers typical of oligodendrocytes (e.g. Olig1, Olig2, Sox10, myelin proteins) or astroglia (e.g. GFAP, EAAT2). Nestin+ and Sox2+ cells continue to be found in the mature CNS, although in more restricted germinal zones (Komitova & Eriksson 2004, Ellis 2004). There is certainly evidence that neural progenitors may have a secretory function. For example, individual NPCs expressing nestin and A2B5 discharge IP-10/CXCL10 and MCP-1/CCL2 after contact with TNF- (Sheng 2005). NPCs also secrete neurotrophins and various other development regulators (Llado 2004, Benoit 2001, Shingo 2001, Taupin 2000), and transplantation of stem cells and/or NPCs boosts their own success (autocrine results), aswell as marketing neuron.[PMC free of charge content] [PubMed] [Google Scholar]Truck Rie A, Harrington PR, Dow A, Robertson K. function to make a maladaptive state, specifically during advancement or regeneration, when progenitors are many. 2003, Torres-Munoz 2001). Neuropathology is normally rather mediated by immediate neurotoxic activities of released viral protein, or secondarily, through dangerous results orchestrated by glial cells (Kaul 2001, Gendelman 1994, Persidsky & Gendelman 2003, Hauser 2007, Brack-Werner 1999, Kramer-Hammerle 2005b). HIV-infected macrophages/microglia achieving the human brain create a tank of viral an infection, and place the groundwork for irritation resulting in neuropathology and cognitive adjustments. chroman 1 Although there is normally little proof that macroglial cells in vivo are productively contaminated by HIV (Kramer-Hammerle et al. 2005b, Brack-Werner 1999, Gorry 2003), activation of astroglia by viral proteins, or by chemicals released from reactive microglia, can amplify human brain irritation and neurotoxic sequelae, and in addition promote infiltration of contaminated monocytes in the periphery. Hence, HIV neuropathology outcomes from collective ramifications of viral protein and inflammatory mediators on many cell types. Astroglia from human beings and rodents secrete chemokine/cytokines in response to HIV-1 transactivator of transcription (Tat) proteins (Nath 1999, El-Hage 2005, Kutsch 2000, McManus 2000, Rappaport 1999, Conant 1998). We’ve proven that Tat-induced [Ca2+]i replies mediate CCL2/MCP-1, CCL5/RANTES and interleukin-6 (IL-6) discharge, leading to downstream signaling through NFB-dependent pathways (El-Hage et al. 2005, El-Hage 2008b). Concurrent contact with morphine exacerbates Tat-induced chemokine/cytokine creation and microglial activation through CCL5/RANTES-driven amplification of CCL2/MCP-1 (El-Hage 2008a, El-Hage 2006a, El-Hage 2006b, Bruce-Keller 2008), an observation that may partially explain fairly high incidences of microglial activation, neuropathology and cognitive disruption among HIV sufferers who mistreatment opiates (Bell 2006, Arango 2004, Anthony 2008, Bouwman 1998, Dougherty 2002). Astroglia may also be delicate to gp120, that may elevate [Ca2+]i (Codazzi 1996, Holden 1999), and alter gene appearance (Wang 2004, Galey 2003) resulting in chemokine/cytokine secretion (Buriani 1999, Kong 1996, Ronaldson & Bendayan 2006, Yeung 1995), with some proof for exacerbation by opioids (Mahajan 2005). Inside our hands, Tat generally elicits even more chemokine/cytokine secretion than gp120, as well as the responsivity varies with human brain regional (Appropriate 2010). Replies of astroglia to various other HIV-1 protein have been much less well examined (Kramer-Hammerle 2005a, Lehmann 2006). We had been intrigued by the chance that much less differentiated CNS cells, furthermore to microglia and astroglia, might secrete inflammatory mediators. This might parallel circumstances chroman 1 in other tissue. Unstimulated bone tissue marrow or cord-derived mesenchymal stem cells secrete a spectral range of chemokine/cytokines and development elements, including multiple FGFs, interleukins, IGF-1, leukemia inhibitory aspect, CCL2/MCP-1, MIP-1, MIP-1, SDF-1, and VEGF (Rafei 2008, Croitoru-Lamoury 2007, Schinkothe 2008, Chen 2008, Liu & Hwang 2005, Wagner 2007). As mesenchymal stem cells differentiate, the total amount of elements released varies with cell destiny (Molloy 2009, Kilroy 2007). Neural progenitor cells (NPCs), which are based on undifferentiated neuroepithelial cells, certainly are a self-renewing and multipotential way to obtain neurons and macroglial cells. Common markers for NPCs are the intermediate filament nestin as well as the transcription aspect Sox2 (sex identifying area of Y (SRY)-related HMG-box gene 2). As NPCs differentiate, they become generally limited to either neuronal or glial fates. Differentiating glial-restricted progenitors (GPCs) exhibit markers usual of oligodendrocytes (e.g. Olig1, Olig2, Sox10, myelin protein) or astroglia (e.g. GFAP, EAAT2). Nestin+ and Sox2+ cells continue being within the older CNS, although in even more restricted germinal areas (Komitova & Eriksson 2004, Ellis 2004). There is certainly proof that neural progenitors may possess a secretory function. For example, individual NPCs expressing nestin and A2B5 discharge IP-10/CXCL10 and MCP-1/CCL2 after contact with TNF- (Sheng 2005). NPCs.2001;46:265C280. procedure that encourages defense inspection of generated cells newly. Pathogens such as for example HIV might usurp this function to make a maladaptive state, specifically during advancement or regeneration, when progenitors are many. 2003, Torres-Munoz 2001). Neuropathology is normally rather mediated by immediate neurotoxic activities of released viral protein, or secondarily, through dangerous results orchestrated by glial cells (Kaul 2001, Gendelman 1994, Persidsky & Gendelman 2003, Hauser 2007, Brack-Werner 1999, Kramer-Hammerle 2005b). HIV-infected macrophages/microglia achieving the human brain create a tank of viral an infection, and place the groundwork for irritation resulting in neuropathology and cognitive adjustments. Although there is normally little proof that macroglial cells in vivo are productively contaminated by HIV (Kramer-Hammerle et al. 2005b, Brack-Werner 1999, Gorry 2003), activation of astroglia by viral proteins, or by chemicals released from reactive microglia, can amplify human brain irritation and neurotoxic sequelae, and in addition promote infiltration of contaminated monocytes in the periphery. Hence, HIV neuropathology outcomes from collective ramifications of viral protein and inflammatory mediators on many cell types. Astroglia from human beings and rodents secrete chemokine/cytokines in response to HIV-1 transactivator of transcription (Tat) proteins (Nath 1999, El-Hage 2005, Kutsch 2000, McManus 2000, Rappaport 1999, Conant 1998). We’ve proven that Tat-induced [Ca2+]i replies mediate CCL2/MCP-1, CCL5/RANTES and interleukin-6 (IL-6) discharge, leading to downstream signaling through NFB-dependent pathways (El-Hage et al. 2005, El-Hage 2008b). Concurrent contact with morphine exacerbates Tat-induced chemokine/cytokine creation and microglial activation through CCL5/RANTES-driven amplification of CCL2/MCP-1 (El-Hage 2008a, El-Hage 2006a, El-Hage 2006b, Bruce-Keller 2008), an observation that may partially explain fairly high incidences of microglial activation, neuropathology and cognitive disruption among HIV sufferers who mistreatment opiates (Bell 2006, Arango 2004, Anthony 2008, Bouwman 1998, Dougherty 2002). Astroglia may also be delicate to gp120, that may elevate [Ca2+]i (Codazzi 1996, Holden 1999), and alter gene appearance (Wang 2004, Galey 2003) resulting in chemokine/cytokine secretion (Buriani 1999, Kong 1996, Ronaldson & Bendayan 2006, Yeung 1995), with some proof for exacerbation by opioids (Mahajan 2005). Inside our hands, Tat generally elicits even more chemokine/cytokine secretion than gp120, as well as the responsivity varies with human brain regional (Appropriate 2010). Replies of astroglia to various other HIV-1 protein have been much less well examined (Kramer-Hammerle 2005a, Lehmann 2006). We had been intrigued by the chance that much less differentiated CNS cells, furthermore to microglia and astroglia, might secrete inflammatory mediators. This might parallel circumstances in other tissue. Unstimulated bone tissue marrow or cord-derived mesenchymal stem cells kanadaptin secrete a spectral range of chemokine/cytokines and development elements, including multiple FGFs, interleukins, IGF-1, leukemia inhibitory aspect, CCL2/MCP-1, MIP-1, MIP-1, SDF-1, and VEGF (Rafei 2008, Croitoru-Lamoury 2007, Schinkothe 2008, Chen 2008, Liu & Hwang 2005, Wagner 2007). As mesenchymal stem cells differentiate, the total amount of elements released varies with cell destiny (Molloy 2009, Kilroy 2007). Neural progenitor cells (NPCs), which are based on undifferentiated neuroepithelial cells, certainly are a self-renewing and multipotential way to obtain neurons and macroglial cells. Common markers for NPCs are the intermediate filament nestin as well as the transcription aspect Sox2 (sex identifying area of Y (SRY)-related HMG-box gene 2). As NPCs differentiate, they become generally restricted to either neuronal or glial fates. Differentiating glial-restricted progenitors (GPCs) express markers common of oligodendrocytes (e.g. Olig1, Olig2, Sox10, myelin proteins) or astroglia (e.g. GFAP, EAAT2). Nestin+ and Sox2+ cells continue to be found in the mature CNS, although in more restricted germinal zones (Komitova & Eriksson 2004, Ellis 2004). There is evidence that neural progenitors may have a secretory role. For example, human NPCs expressing nestin and A2B5 release IP-10/CXCL10 and MCP-1/CCL2 after exposure to TNF- (Sheng 2005). NPCs also secrete neurotrophins and other growth regulators (Llado 2004, Benoit.[PubMed] [Google Scholar]McManus CM, Weidenheim K, Woodman SE, Nunez J, Hesselgesser J, Nath A, Berman JW. adaptive process that encourages immune inspection of newly generated cells. Pathogens such as HIV might usurp this function to create a maladaptive state, especially during development or regeneration, when progenitors are numerous. 2003, Torres-Munoz 2001). Neuropathology is usually instead mediated by direct neurotoxic actions of released viral proteins, or secondarily, through toxic effects orchestrated by glial cells (Kaul 2001, Gendelman 1994, Persidsky & Gendelman 2003, Hauser 2007, Brack-Werner 1999, Kramer-Hammerle 2005b). HIV-infected macrophages/microglia reaching the brain create a reservoir of viral contamination, and lay the groundwork for inflammation leading to neuropathology and cognitive changes. Although there is usually little evidence that macroglial cells in vivo are productively infected by HIV (Kramer-Hammerle et al. 2005b, Brack-Werner 1999, Gorry 2003), activation of astroglia by viral proteins, or by substances released from reactive microglia, can amplify brain inflammation and neurotoxic sequelae, and also promote infiltration of infected monocytes from the periphery. Thus, HIV neuropathology results from collective effects of viral proteins and inflammatory mediators on several cell types. Astroglia from humans and rodents secrete chemokine/cytokines in response to HIV-1 transactivator of transcription (Tat) protein (Nath 1999, El-Hage 2005, Kutsch 2000, McManus 2000, Rappaport 1999, Conant 1998). We have shown that Tat-induced [Ca2+]i responses mediate CCL2/MCP-1, CCL5/RANTES and interleukin-6 (IL-6) release, resulting in downstream signaling through NFB-dependent pathways (El-Hage et al. 2005, El-Hage 2008b). Concurrent exposure to morphine exacerbates Tat-induced chemokine/cytokine production and microglial activation through CCL5/RANTES-driven amplification of CCL2/MCP-1 (El-Hage 2008a, El-Hage 2006a, El-Hage 2006b, Bruce-Keller 2008), an observation that may partly explain relatively high incidences of microglial activation, neuropathology and cognitive disturbance among HIV patients who abuse opiates (Bell 2006, Arango 2004, Anthony 2008, Bouwman 1998, Dougherty 2002). Astroglia are also sensitive to gp120, which can elevate [Ca2+]i (Codazzi 1996, Holden 1999), and alter gene expression (Wang 2004, Galey 2003) leading to chemokine/cytokine secretion (Buriani 1999, Kong 1996, Ronaldson & Bendayan 2006, Yeung 1995), with some evidence for exacerbation by opioids (Mahajan 2005). In our hands, Tat generally elicits more chemokine/cytokine secretion than gp120, and the responsivity varies with brain regional (Fitting 2010). Responses of astroglia to other HIV-1 proteins have been less well studied (Kramer-Hammerle 2005a, Lehmann 2006). We were intrigued by the possibility that less differentiated CNS cells, in addition to microglia and astroglia, might secrete inflammatory mediators. This would parallel situations in other tissues. Unstimulated bone marrow or cord-derived mesenchymal stem cells secrete a spectrum of chemokine/cytokines and growth factors, including multiple FGFs, interleukins, IGF-1, leukemia inhibitory factor, CCL2/MCP-1, MIP-1, MIP-1, SDF-1, and VEGF (Rafei 2008, Croitoru-Lamoury 2007, Schinkothe 2008, Chen 2008, Liu & Hwang 2005, Wagner 2007). As mesenchymal stem cells differentiate, the balance of factors released varies with cell fate (Molloy 2009, Kilroy 2007). Neural progenitor cells (NPCs), which derive from undifferentiated neuroepithelial cells, are a self-renewing and multipotential source of neurons and macroglial cells. Common markers for NPCs include the intermediate filament nestin and the transcription factor Sox2 (sex determining region of Y (SRY)-related HMG-box gene 2). As NPCs differentiate, they become largely restricted to either neuronal or glial fates. Differentiating glial-restricted progenitors (GPCs) express markers common of oligodendrocytes (e.g. Olig1, Olig2, Sox10, myelin proteins) or astroglia (e.g. GFAP, EAAT2). Nestin+ and Sox2+ cells continue to be found in the mature CNS, although in more restricted germinal zones (Komitova & Eriksson 2004, Ellis 2004). There is evidence that neural progenitors may have a secretory role. For example, human NPCs expressing nestin and A2B5 release IP-10/CXCL10 and MCP-1/CCL2 after exposure to TNF- (Sheng 2005). NPCs also secrete neurotrophins and other growth regulators (Llado 2004, Benoit 2001, Shingo 2001, Taupin 2000), and transplantation of stem cells and/or NPCs increases their own survival (autocrine effects), as well as promoting neuron survival after.