Gene Set: COATES_MACROPHAGE_M1_VS_M2_DN

Standard name COATES_MACROPHAGE_M1_VS_M2_DN
Systematic name M14515
Brief description Down-regulated genes distinguishing between M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophage subtypes.
Full description or abstract In addition to the directly mutagenic effects of energy deposition in DNA, ionizing radiation is associated with a variety of untargeted and delayed effects that result in ongoing bone marrow damage. Delayed effects are genotype dependent with CBA/Ca mice, but not C57BL/6 mice, susceptible to the induction of damage and also radiation-induced acute myeloid leukemia. Because macrophages are a potential source of ongoing damaging signals, we have determined their gene expression profiles and we show that bone marrow-derived macrophages show widely different intrinsic expression patterns. The profiles classify macrophages derived from CBA/Ca mice as M1-like (pro-inflammatory) and those from C57BL/6 mice as M2-like (anti-inflammatory); measurements of NOS2 and arginase activity in normal bone marrow macrophages confirm these findings. After irradiation in vivo, but not in vitro, C57BL/6 macrophages show a reduction in NOS2 and an increase in arginase activities, indicating a further M2 response, whereas CBA/Ca macrophages retain an M1 phenotype. Activation of specific signal transducer and activator of transcription signaling pathways in irradiated hemopoietic tissues supports these observations. The data indicate that macrophage activation is not a direct effect of radiation but a tissue response, secondary to the initial radiation exposure, and have important implications for understanding genotype-dependent responses and the mechanisms of the hemotoxic and leukemogenic consequences of radiation exposure.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18199539   Authors: Coates PJ,Rundle JK,Lorimore SA,Wright EG
Exact source Table 1S: fold change < -2
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_Mouse430
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Version history 3.0: First introduced

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