PMID- 28583844
OWN - NLM
STAT- MEDLINE
DCOM- 20170818
LR  - 20231213
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 140
DP  - 2017 Sep 15
TI  - Nociceptin/orphanin FQ antagonizes lipopolysaccharide-stimulated proliferation, 
      migration and inflammatory signaling in human glioblastoma U87 cells.
PG  - 89-104
LID - S0006-2952(17)30323-4 [pii]
LID - 10.1016/j.bcp.2017.05.021 [doi]
AB  - Glioblastoma is among the most aggressive brain tumors and has an exceedingly 
      poor prognosis. Recently, the importance of the tumor microenvironment in 
      glioblastoma cell growth and progression has been emphasized. Toll-like receptor 
      4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and endogenous ligands 
      originating from dying cells or the extracellular matrix involved in host defense 
      and in inflammation. G-protein coupled receptors (GPCRs) have gained interest in 
      anti-tumor drug discovery due to the role that they directly or indirectly play 
      by transactivating other receptors, causing cell migration and proliferation. A 
      proteomic analysis showed that the nociceptin receptor (NOPr) is among the GPCRs 
      significantly expressed in glioblastoma cells, including U87 cells. We describe a 
      novel role of the peptide nociceptin (N/OFQ), the endogenous ligand of the NOPr 
      that counteracts cell migration, proliferation and increase in IL-1beta mRNA 
      elicited by LPS via TLR4 in U87 glioblastoma cells. Signaling pathways through 
      which N/OFQ inhibits LPS-mediated cell migration and elevation of [Ca(2+)](i) 
      require beta-arrestin 2 and are sensitive to TNFR-associated factor 6, c-Src and 
      protein kinase C (PKC). LPS-induced cell proliferation and increase in IL-1beta mRNA 
      are counteracted by N/OFQ via beta-arrestin 2, PKC and extracellular 
      signal-regulated kinase 1/2; furthermore, the contributions of the transcription 
      factors NF-kB and AP-1 were investigated. Independent of LPS, N/OFQ induces a 
      significant increase in cell apoptosis. Contrary to what was observed in other 
      cell models, a prolonged exposure to this endotoxin did not promote any tolerance 
      of the cellular effects above described, including NOPr down-regulation while 
      N/OFQ loses its inhibitory role.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Bedini, Andrea
AU  - Bedini A
AD  - Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 
      40126 Bologna, Italy.
FAU - Baiula, Monica
AU  - Baiula M
AD  - Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 
      40126 Bologna, Italy.
FAU - Vincelli, Gabriele
AU  - Vincelli G
AD  - Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 
      40126 Bologna, Italy.
FAU - Formaggio, Francesco
AU  - Formaggio F
AD  - Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 
      40126 Bologna, Italy.
FAU - Lombardi, Sara
AU  - Lombardi S
AD  - Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 
      40126 Bologna, Italy.
FAU - Caprini, Marco
AU  - Caprini M
AD  - Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 
      40126 Bologna, Italy.
FAU - Spampinato, Santi
AU  - Spampinato S
AD  - Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 
      40126 Bologna, Italy. Electronic address: santi.spampinato@unibo.it.
LA  - eng
PT  - Journal Article
DEP - 20170602
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (ARRB2 protein, human)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (IL1B protein, human)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Opioid Peptides)
RN  - 0 (Receptors, Opioid)
RN  - 0 (TLR4 protein, human)
RN  - 0 (TNF Receptor-Associated Factor 6)
RN  - 0 (Tifab protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (beta-Arrestin 2)
RN  - 0 (lipopolysaccharide, Escherichia coli O111 B4)
RN  - 0 (Nociceptin Receptor)
RN  - 0 (OPRL1 protein, human)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Astrocytes/drug effects/immunology/metabolism/pathology
MH  - Calcium Signaling/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Gene Expression Regulation, Neoplastic
MH  - Glioblastoma/*drug therapy/immunology/metabolism/pathology
MH  - Humans
MH  - Interleukin-1beta/agonists/antagonists & inhibitors/genetics/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Ligands
MH  - Lipopolysaccharides/antagonists & inhibitors/toxicity
MH  - Neoplasm Proteins/agonists/antagonists & inhibitors/metabolism
MH  - Nerve Tissue Proteins/agonists/antagonists & inhibitors/metabolism
MH  - Opioid Peptides/*pharmacology
MH  - RNA Interference
MH  - Receptors, Opioid/agonists/genetics
MH  - TNF Receptor-Associated Factor 6/*agonists/antagonists & 
      inhibitors/genetics/metabolism
MH  - Toll-Like Receptor 4/agonists/*antagonists & inhibitors/genetics/metabolism
MH  - beta-Arrestin 2/*agonists/antagonists & inhibitors/genetics/metabolism
MH  - Nociceptin Receptor
MH  - Nociceptin
OTO - NOTNLM
OT  - Apoptosis
OT  - Cell migration
OT  - Cell proliferation
OT  - Glioblastoma
OT  - Nociceptin
EDAT- 2017/06/07 06:00
MHDA- 2017/08/19 06:00
CRDT- 2017/06/07 06:00
PHST- 2017/02/14 00:00 [received]
PHST- 2017/05/31 00:00 [accepted]
PHST- 2017/06/07 06:00 [pubmed]
PHST- 2017/08/19 06:00 [medline]
PHST- 2017/06/07 06:00 [entrez]
AID - S0006-2952(17)30323-4 [pii]
AID - 10.1016/j.bcp.2017.05.021 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2017 Sep 15;140:89-104. doi: 10.1016/j.bcp.2017.05.021. Epub 
      2017 Jun 2.