Regulation of IL-10 expression by upstream stimulating factor (USF-1) in glioma-associated microglia.
Understanding the local CNS immune response to neoplasms is essential in the development of immune-based treatments for malignant brain tumors. Using rodent glioma models, we have recently found tumor-associated microglia/macrophages (MG/MP) to be less responsive to known MG/MP activators such as CpG, LPS and IFN-gamma. To understand the mechanism of MG/MP suppression, nuclear extracts from rodent intracranial C6 gliomas, C6 glioma-associated MG/MP, normal brain, and normal MG/MP were obtained and studied using Electrophoretic Mobility Shift Assay (EMSA). Among the nuclear factors studied (AP-1, IRF, USF-1 and Stat-1) only USF-1, which is constitutively expressed in most cells, was down-regulated in tumor-associated MG/MP, but not normal MG/MP. Because tumor-associated MG/MP had higher expression of IL-10 (but not TNF-alpha or TGF-beta), we evaluated the role of USF-1 on IL-10 expression. siRNA mediated inhibition of USF-1 expression in primary MG/MP cultures resulted in up-regulation of IL-10 mRNA but not TNF-alpha or TGF-beta. These findings suggest that USF-1 may play a role in IL-10 regulation in MG/MP in brain tumors.
Zhang
Leying
L
Department of Neurosurgery, Beckman Research Institute, City of Hope National Medical Center, CA 91010, USA.
Handel
Michelle Van
MV
Schartner
Jill M
JM
Hagar
Aaron
A
Allen
Grant
G
Curet
Marjorie
M
Badie
Behnam
B
D000704:Analysis of Variance; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D002478:Cells, Cultured; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051720:Upstream Stimulatory Factors / Q000494:pharmacology*
D034741:RNA, Small Interfering; D051720:Upstream Stimulatory Factors; C497182:Usf1 protein, rat; D016753:Interleukin-10