PMID- 18832699
OWN - NLM
STAT- MEDLINE
DCOM- 20081021
LR  - 20190516
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 181
IP  - 8
DP  - 2008 Oct 15
TI  - Astrocytic regulation of human monocytic/microglial activation.
PG  - 5425-32
AB  - Recent reports have described reduced immunological responsiveness and 
      stimulatory capacity among monocytes/microglia that infiltrate malignant human 
      gliomas. Herein, we demonstrate that culture of ex vivo human monocytes or 
      primary human microglia with tumor cells isolated from glioblastoma multiforme 
      (GBM) specimens renders them tolerogenic, capable of suppressing the function of 
      ex vivo monocytes in the absence of tumor cells or their soluble factors. We 
      demonstrate that the tolerance induced in monocytes/microglia by GBM tumor cells 
      is not associated with interference with the signaling cascade associated with 
      TLR- or CD40-induced monocyte activation. Rather, these tumor cells appear to 
      up-regulate pathways that antagonize positive signaling pathways, including but 
      not limited to STAT3 and STAT5. Finally, we demonstrate that the tolerogenic 
      properties of GBM tumor cells amplify properties inherent to nontransformed 
      astrocytes. Future studies that identify all of the molecular mechanisms by which 
      astrocytes and malignant gliomas suppress monocyte/microglial function will have 
      dual therapeutic benefits: suppressing these pathways may benefit patients with 
      astrocytic tumors, while enhancing them may benefit patients with autoimmune 
      processes within the CNS, such as multiple sclerosis.
FAU - Kostianovsky, Alex M
AU  - Kostianovsky AM
AD  - Department of Neurology, Center for Neurologic Diseases, Brigham and Women's 
      Hospital and Harvard Medical School, Boston, MA 02115, USA.
FAU - Maier, Lisa M
AU  - Maier LM
FAU - Anderson, Richard C
AU  - Anderson RC
FAU - Bruce, Jeffrey N
AU  - Bruce JN
FAU - Anderson, David E
AU  - Anderson DE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD40 Antigens)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Astrocytes/*immunology/metabolism/pathology
MH  - CD40 Antigens/immunology
MH  - Glioma/*immunology/pathology/therapy
MH  - Humans
MH  - Microglia/*immunology/pathology
MH  - Monocytes/*immunology/pathology
MH  - Multiple Sclerosis/immunology/pathology/therapy
MH  - STAT3 Transcription Factor/immunology
MH  - STAT5 Transcription Factor/immunology
MH  - Signal Transduction/immunology
MH  - Toll-Like Receptors/immunology
MH  - Tumor Cells, Cultured
EDAT- 2008/10/04 09:00
MHDA- 2008/10/22 09:00
CRDT- 2008/10/04 09:00
PHST- 2008/10/04 09:00 [pubmed]
PHST- 2008/10/22 09:00 [medline]
PHST- 2008/10/04 09:00 [entrez]
AID - 181/8/5425 [pii]
AID - 10.4049/jimmunol.181.8.5425 [doi]
PST - ppublish
SO  - J Immunol. 2008 Oct 15;181(8):5425-32. doi: 10.4049/jimmunol.181.8.5425.