4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) suppresses HIV1-gp120 mediated production of IL6 and IL8 but not CCL5

• Published in: Scientific reports 2017-08, Vol.7 (1), p.8129-12, Article 8129
• Main Authors: Abdalla, Fatma, Nookala, Anantha, Padhye, Subhash B., Kumar, Anil, Bhat, Hari K.
• Format: Article
• Language: English
• Subjects: 631/378/1689; 692/617/375; 82; 82/29; 82/51; 82/80; 96; 96/1; 96/106; 96/109; 96/21; Active Transport, Cell Nucleus - drug effects; AKT protein; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Cell Line; Chemokine CCL5 - biosynthesis; Chemokine CCL5 - genetics; Chemotherapy; Gene expression; Gene Expression - drug effects; Glycoprotein gp120; HIV; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - metabolism; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Inflammation; Interleukin 6; Interleukin 8; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; MAP kinase; mRNA; multidisciplinary; NF-κB protein; Nuclear transport; Phosphorylation; Phosphorylation - drug effects; Protein expression; Proteins; Resveratrol; Resveratrol - pharmacology; Science; Science (multidisciplinary); Stat3 protein; STAT3 Transcription Factor - metabolism; Stilbenes - pharmacology; Transcription Factor RelA - metabolism; Transcription factors; Transfection; Translocation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-08332-z

Human immunodeficiency virus (HIV) has been associated with inflammatory effects that may potentially result in neurodegenerative changes and a number of newer chemotherapeutic agents are being tested to ameliorate these effects. In this study, we investigated the anti-neuroinflammatory activity of a novel resveratrol analog 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) against HIV1-gp120 induced neuroinflammation in SVG astrocytes. SVG astrocytic cells were pretreated with TIMBD or resveratrol (RES) and then transfected with a plasmid encoding HIV1-gp120. The mRNA and protein expression levels of proinflammatory cytokines IL6, IL8 and CCL5 were determined. Protein expression levels of NF-κB, AP1, p-STAT3, p-AKT, p-IKKs and p-p38 MAPK were also determined. TIMBD inhibited gp120-induced RNA and protein expression levels of IL6 and IL8, but not that of CCL5 in SVG astrocytes. Moreover, TIMBD attenuated gp120-induced phosphorylation of cJUN, cFOS, STAT3, p38-MAPK, AKT and IKKs, and the nuclear translocation of NF-κB p-65 subunit whereas RES mostly affected NF-κB protein expression levels. Our results suggest that TIMBD exerts anti-inflammatory effects better than that of RES in SVG astrocytes in vitro . These effects seem to be regulated by AP1, STAT-3 and NF-κB signaling pathways. TIMBD may thus have a potential of being a novel agent for treating HIV1-gp120-mediated neuroinflammatory diseases.