TY - JOUR
T1 - Nitrosporeusine analogue ameliorates Chandipura virus induced inflammatory response in CNS via NFκb inactivation in microglia
AU - Verma, Abhishek Kumar
AU - Waghmare, Trushnal Shrikant
AU - Jachak, Gorakhnath R.
AU - Philkhana, Satish Chandra
AU - Reddy, Srinivasa
PY - 2018/7/12
Y1 - 2018/7/12
N2 - Chandipura Virus (CHPV), a negative-stranded RNA virus belonging to the Rhabdoviridae family, has been previously reported to bring neuronal apoptosis by activating several factors leading to neurodegeneration. Following virus infection of the central nervous system, microglia, the ontogenetic and functional equivalents of macrophages in somatic tissues gets activated and starts secreting chemokines, thereby recruiting peripheral leukocytes into the brain parenchyma. In the present study, we have systemically examined the effect of CHPV on microglia and the activation of cellular signalling pathways leading to chemokine expression upon CHPV infection. Protein and mRNA expression profiles of chemokine genes revealed that CHPV infection strongly induces the expression of CXC chemokine ligand 10 (CXCL10) and CC chemokine ligand 5 (CCL5) in microglia. CHPV infection triggered the activation of signalling pathways mediated by mitogen-activated protein kinases, including p38, JNK 1 and 2, and nuclear factor κB (NF-kappaB). CHPV-induced expression of CXCL10 and CCL5 was achieved by the activation of p38 and NF-kappaB pathways. Considering the important role of inflammation in neurodegeneration, we have targeted NF-kappaB using a newly synthesised natural product nitrosporeusine analogue and showed incapability of microglial supernatant of inducing apoptosis in neurons after treatment
AB - Chandipura Virus (CHPV), a negative-stranded RNA virus belonging to the Rhabdoviridae family, has been previously reported to bring neuronal apoptosis by activating several factors leading to neurodegeneration. Following virus infection of the central nervous system, microglia, the ontogenetic and functional equivalents of macrophages in somatic tissues gets activated and starts secreting chemokines, thereby recruiting peripheral leukocytes into the brain parenchyma. In the present study, we have systemically examined the effect of CHPV on microglia and the activation of cellular signalling pathways leading to chemokine expression upon CHPV infection. Protein and mRNA expression profiles of chemokine genes revealed that CHPV infection strongly induces the expression of CXC chemokine ligand 10 (CXCL10) and CC chemokine ligand 5 (CCL5) in microglia. CHPV infection triggered the activation of signalling pathways mediated by mitogen-activated protein kinases, including p38, JNK 1 and 2, and nuclear factor κB (NF-kappaB). CHPV-induced expression of CXCL10 and CCL5 was achieved by the activation of p38 and NF-kappaB pathways. Considering the important role of inflammation in neurodegeneration, we have targeted NF-kappaB using a newly synthesised natural product nitrosporeusine analogue and showed incapability of microglial supernatant of inducing apoptosis in neurons after treatment
KW - Chandipura virus
KW - Microglia
KW - Inflammation
UR - https://www-scopus-com.db.rsu.lv/record/display.uri?eid=2-s2.0-85051286312&origin=resultslist&sort=plf-f&src=s&sid=4e71486c953ed56e5167c1ee0d80e32d&sot=b&sdt=b&s=TITLE%28Nitrosporeusine+analogue+ameliorates+Chandipura+virus+induced+inflammatory+response+in+CNS+via+NF%CE%BAb+inactivation+in+microglia%29&sl=132&sessionSearchId=4e71486c953ed56e5167c1ee0d80e32d&relpos=0
M3 - Review article
SN - 1935-2727
VL - 12
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 7
M1 - e0006648
ER -