Table 2.
Astrocyte responses to HIV-1-relevant and METH stimuli.
| Outcomes | HIV-1-relevant stimuli and METH | Regulation or mechanism | References |
|---|---|---|---|
| BBB PERMEABILITY | |||
| Increased CXCL10 expression, PBMC chemotactic activity | Virus, TNF-α | TNFR 1/2 | van Marle et al., 2004 |
| Virus, IL-1β, TNF-α | CXCR3/CXCR4, MAPK, PKC | Mehla et al., 2012 | |
| Tat1−72 treatment | p38 MAPK | Kutsch et al., 2000 | |
| Increased CCL2, CXCL8, CXCL10, ICAM-1 and vascular (V)CAM-1 expression | Tat treatment | MAPK, JNK, AP-1, NF-κB | Youn et al., 2014 |
| Increased ICAM-1 expression leading to enhanced interactions with MP | gp120 treatment | PKC, TK, JAK2/STAT1α | Shrikant et al., 1996 |
| Increased TNF-α expression leading to BBB impairment | METH | NF-κB pathway | Coelho-Santos et al., 2015 |
| Dysregulation of TIMP-1: MMP Balance | Virus, IL-1β | CAATT-enhancer binding protein (C/EBP)-β, ERK 1/2, p38 MAPK | Suryadevara et al., 2003; Fields et al., 2011, 2013 |
| IL-1β | NF-κB, AP-1, PI3K, MAPK | Yang et al., 2015 | |
| PRO-INFLAMMATORY | |||
| Viral replication | |||
| Increased pro-viral replication (FIV) | METH | Viral entry or integration | Gavrilin et al., 2002 |
| Increased pro-viral replication (HIV) | IFN-γ | STAT3 and Dickkopf-related protein 1, β-catenin | Li et al., 2011 |
| Cytokines and chemokine expression | |||
| Increased CCL2 production leading to regulation of IFN-α/β and TRAIL expression in MP | Virus (SIV) | Zaritsky et al., 2012 | |
| Increased C3 expression | Virus, Nef, gp41 treatment | Activation of adenylate cyclase, increased cAMP, IL-6/IL-1β responsive promoter elements and C/EBP-δ | Speth et al., 2002; Bruder et al., 2004 |
| Increased C5, IL-1β, IL-1ra, TNF-α, CXCL10, CCL3, CCL5 | IL-1β, TNF-α | NF-κB | Choi et al., 2014 |
| Increased CCL20 expression | IL-1β, TNF-α | Ambrosini et al., 2003 | |
| Increased CCL5 expression | Nef treatment | Akt, p38 MAPK, NF-κB, C/EBP and AP-1 | Liu et al., 2014a |
| IL-1β, IFN-γ/β | IκBα, MAPKs, C/EBP-β, STAT1/2, interferon regulatory factor-1 (IRF-1) | Kim et al., 2004 | |
| Increased CCL2 expression | TNF-α | AEG-1 expression | Vartak-Sharma et al., 2014 |
| Increased CCL7 expression | TNF-α | Renner et al., 2011 | |
| Increased CX3CL1 expression | TNF-α | Yoshida et al., 2001 | |
| Increased CCL2, CXCL8 and CD38 expression | HIV-1YU−2 expression | MAPK, ERK 1/2, NF-κB | Kou et al., 2009; Mamik et al., 2011 |
| Increased CCL2, CXCL8 and CXCL10 expression | Tat treatment | MAPK, JNK, AP-1, NF-κB | Youn et al., 2014 |
| Increased CCL2 and CXCL8 expression | Tat1−72 treatment | Mitogen-activated protein kinase kinase (MEK) ½ | Kutsch et al., 2000 |
| Increased CCL2, CXCL8 and IL-6 expression | VPR treatment | Ferrucci et al., 2013 | |
| Increased CXCL8 and CXCL10 expression | Virus, VPR treatment | Vivithanaporn et al., 2010 | |
| Increased CXCL8 and IL-6 expression | Tat expression | PI3K/Akt, p38 MAPK and NF-κB, p38δ, AP-1 | Nookala and Kumar, 2014 |
| METH | mGluR5, Akt/PI3K, NF-κB | Shah et al., 2012b | |
| Increased IL-6 and TNF-α expression | gp120 treatment | Van der Meide and Schellekens, 1996 | |
| Increased IL-6 expression | gp120 treatment | IκB kinase (IKK)β and NF-κB | Shah et al., 2011 |
| Eicosanoid expression and regulation | |||
| Increased TNF-α, IL-1β, leukotriene B4, leukotriene D4, lipoxin A4 and platelet-activating factor (PAF) expression | Virus (HIV-infected MP) coculture | Astrocyte cellular contact, AA-dependent | Genis et al., 1992 |
| Increased prostaglandin EP3R expression | IL-1β | PKC, NF-κB | Waschbisch et al., 2006 |
| Increased COX-2 expression | IL-1β | C/EBP-β | Fields and Ghorpade, 2012 |
| Increased PGE2 expression | gp120 treatment | NO | Mollace et al., 1994 |
| Increased COX-2, PGE2 and thromboxane A2 receptor expression | gp120 treatment (Clade B) | Samikkannu et al., 2011 | |
| Increased COX-2 and PGE2 expression | Tat treatment | NFAT, AP-1 | Blanco et al., 2008 |
| Increased IL-6, COX-2, PGE2 expression | IL-1β, TNF-α | p38 MAPK | Falsig et al., 2004 |
| OXIDATIVE STRESS | |||
| Increased ROS and NRF-2 anti-oxidant gene expression | gp120BAL treatment | Reddy et al., 2012 | |
| Increased intracellular pH | gp120 treatment, IL-1β, TNF-α, IFN-γ | Na+/H+ exchange | Benos et al., 1994 |
| Decreased DRD2 and DAT expression | gp120 treatment (Clade B), METH | CREB, CAMKII, CAMKIV | Samikkannu et al., 2015 |
| Decreased ATP and GSH leading to increased ROS | VPR treatment | Ferrucci et al., 2013 | |
| Increased mitochondria depolarization | METH | ROS | Lau et al., 2000 |
| Increased iNOS expression and NO levels | IL-1β, TNF-α, IFN-γ | p38 MAPK | Falsig et al., 2004 |
| Increased iNOS expression | IFN-γ, IFN-β, LPS | Mohsenzadegan et al., 2015 | |
| EXCITOTOXICITY AND NEURAL CELL TOXICITY | |||
| Decreased EAAT-2 expression and function | HIV-1JR−FL, IL-1β, METH | TAAR1, cAMP | Cisneros and Ghorpade, 2012, 2014 |
| IL-1β | AEG-1 | Vartak-Sharma et al., 2014 | |
| Decreased NMDA receptor expression and glutamine levels | gp120 treatment (Clade B) | Samikkannu et al., 2011 | |
| Increased CXCL10 expression leading to neuronal toxicity | Virus, NefYU−2 expression, TNF-α | TNFR1/2 | van Marle et al., 2004 |
| Virus, IL-1β, TNF-α | CXCR3/CXCR4, MAPK, PKC | Mehla et al., 2012 | |
| IL-1β, α-synuclein | Tousi et al., 2012 | ||
| Increased astrocyte apoptosis | gp120 treatment | Van der Meide and Schellekens, 1996 | |
| IL-1β, TNF-α, IFN-γ | CD95, caspase 8, FADD | Falsig et al., 2004; Gardner et al., 2006 | |
| ASTROGLIAL PHYSIOLOGICAL FUNCTIONS | |||
| Neurotrophic | |||
| Increased BDNF expression | TNF-α | NF-αB, C/EBP-β with ERK MAPK | Saha et al., 2006 |
| Glutamate | PLC, IP3, internal stores of Ca2+ | Jean et al., 2008 | |
| Anti-inflammatory | |||
| Reduced eicosanoids, platelet-activating factor (PAF) and TNF-α | Virus (HIV-infected MP) coculture | Astrocyte cellular contact | Nottet et al., 1995 |
| Decreased viral replication in MP | Virus (M tropic) | Latent TGF-β expression in astrocytes | da Cunha et al., 1995; Hori et al., 1999 |
| Increased TGF-β1 | Tat treatment and expression | Wahl et al., 1991; Cupp et al., 1993; Rasty et al., 1996; Thatikunta et al., 1997 | |
| Decreased IL-1β-induced TIMP-1 and MMP-2 expression, increased ECM levels | IL-1β | TGF-β 1/2 | Wyss-Coray et al., 1995; Dhar et al., 2006 |
| Increased IL-10 expression | gp41 treatment | adenylate cyclase, cAMP | Speth et al., 2000 |
| IFN-γ/β, LPS | Mohsenzadegan et al., 2015 | ||