Open Access4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) suppresses HIV1-gp120 mediated production of IL6 and IL8 but not CCL5
Author(s) -
Fatma Abdalla,
Anantha Nookala,
Subhash Padhyé,
Anil Kumar,
Hari K. Bhat
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-08332-z
Subject(s) - ccl3 , protein kinase b , proinflammatory cytokine , p38 mitogen activated protein kinases , ccl5 , nf κb , interleukin 8 , mapk/erk pathway , signal transduction , microbiology and biotechnology , cancer research , chemokine , chemistry , biology , cytokine , immunology , ccl2 , inflammation , t cell , immune system , il 2 receptor
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.