PMID- 26427514
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 32
DP  - 2015 Oct 20
TI  - Down-regulation of IKKbeta expression in glioma-infiltrating microglia/macrophages 
      is associated with defective inflammatory/immune gene responses in glioblastoma.
PG  - 33077-90
LID - 10.18632/oncotarget.5310 [doi]
AB  - Glioblastoma (GBM) is an aggressive malignancy associated with profound host 
      immunosuppression. Microglia and macrophages infiltrating GBM acquire the 
      pro-tumorigenic, M2 phenotype and support tumor invasion, proliferation, 
      survival, angiogenesis and block immune responses both locally and 
      systematically. Mechanisms responsible for immunological deficits in GBM patients 
      are poorly understood. We analyzed immune/inflammatory gene expression in five 
      datasets of low and high grade gliomas, and performed Gene Ontology and signaling 
      pathway analyses to identify defective transcriptional responses. The expression 
      of many immune/inflammatory response and TLR signaling pathway genes was reduced 
      in high grade gliomas compared to low grade gliomas. In particular, we found the 
      reduced expression of the IKBKB, a gene coding for IKKbeta, which phosphorylates IkappaB 
      proteins and represents a convergence point for most signal transduction pathways 
      leading to NFkappaB activation. The reduced IKBKB expression and IKKbeta levels in GBM 
      tissues were demonstrated by qPCR, Western blotting and immunohistochemistry. The 
      IKKbeta expression was down-regulated in microglia/macrophages infiltrating 
      glioblastoma. NFkappaB activation, prominent in microglia/macrophages infiltrating 
      low grade gliomas, was reduced in microglia/macrophages in glioblastoma tissues. 
      Down-regulation of IKBKB expression and NFkappaB signaling in microglia/macrophages 
      infiltrating glioblastoma correlates with defective expression of 
      immune/inflammatory genes and M2 polarization that may result in the global 
      impairment of anti-tumor immune responses in glioblastoma.
FAU - Mieczkowski, Jakub
AU  - Mieczkowski J
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Kocyk, Marta
AU  - Kocyk M
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
AD  - Postgraduate School of Molecular Medicine, Medical University of Warsaw, Poland.
FAU - Nauman, Pawel
AU  - Nauman P
AD  - Department of Neurosurgery, Institute Psychiatry and Neurology, Warsaw, Poland.
FAU - Gabrusiewicz, Konrad
AU  - Gabrusiewicz K
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Sielska, Malgorzata
AU  - Sielska M
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Przanowski, Piotr
AU  - Przanowski P
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Maleszewska, Marta
AU  - Maleszewska M
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Rajan, Wenson D
AU  - Rajan WD
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Pszczolkowska, Dominika
AU  - Pszczolkowska D
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
FAU - Tykocki, Tomasz
AU  - Tykocki T
AD  - Department of Neurosurgery, Institute Psychiatry and Neurology, Warsaw, Poland.
FAU - Grajkowska, Wieslawa
AU  - Grajkowska W
AD  - Department of Pathology, The Children's Memorial Health Institute, Warsaw, 
      Poland.
FAU - Kotulska, Katarzyna
AU  - Kotulska K
AD  - Deparment of Neurology, The Children's Memorial Health Institute, Warsaw, Poland.
FAU - Roszkowski, Marcin
AU  - Roszkowski M
AD  - Deparment of Neurosurgery, The Children's Memorial Health Institute, Warsaw, 
      Poland.
FAU - Kostkiewicz, Boguslaw
AU  - Kostkiewicz B
AD  - Central Clinical Hospital Ministry of Interior, Warsaw, Poland.
FAU - Kaminska, Bozena
AU  - Kaminska B
AD  - Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, 
      Warsaw, Poland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/enzymology/genetics/immunology/*pathology
MH  - Down-Regulation
MH  - Gene Expression Profiling
MH  - Glioblastoma/enzymology/genetics/immunology/*pathology
MH  - Humans
MH  - I-kappa B Kinase/genetics/*metabolism
MH  - Macrophages/enzymology/immunology/metabolism/*pathology
MH  - Male
MH  - Microglia/enzymology/immunology/metabolism/*pathology
MH  - Rats
MH  - Rats, Wistar
PMC - PMC4741750
OTO - NOTNLM
OT  - IKKbeta/NFkB signaling
OT  - glioblastoma
OT  - glioma-associated microglia/macrophages
OT  - global gene expression profiling
OT  - immunosuppression
COIS- CONFLICTS OF INTEREST The authors declare no competing financial interests.
EDAT- 2015/10/03 06:00
MHDA- 2016/09/23 06:00
PMCR- 2015/10/20
CRDT- 2015/10/03 06:00
PHST- 2015/04/03 00:00 [received]
PHST- 2015/09/15 00:00 [accepted]
PHST- 2015/10/03 06:00 [entrez]
PHST- 2015/10/03 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
PHST- 2015/10/20 00:00 [pmc-release]
AID - 5310 [pii]
AID - 10.18632/oncotarget.5310 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Oct 20;6(32):33077-90. doi: 10.18632/oncotarget.5310.