Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.
We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment.
Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Republic of Korea.
Ji-Sun
JS
Hwang
Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Republic of Korea.
Eun-Hye
EH
Jung
Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Republic of Korea.
Mi-Youn
MY
Kwon
Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Republic of Korea. Electronic address: iohan@inha.ac.kr.
Inn-Oc
IO
Han
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007231:Infant, Newborn; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D009573:Nitrites / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D007093:Imidazoles; D053583:Interleukin-1beta; D009573:Nitrites; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
Glioma; Interleukin-1beta; Microglia; Tumor necrosis factor-alpha