Interleukin-10 expression in macrophages during phagocytosis of apoptotic cells is mediated by homeodomain proteins Pbx1 and Prep-1. Immunity 2007 Dec;27(6):952-64
Date
12/21/2007Pubmed ID
18093541Pubmed Central ID
PMC2194654DOI
10.1016/j.immuni.2007.11.014Scopus ID
2-s2.0-37049031230 (requires institutional sign-in at Scopus site) 200 CitationsAbstract
Production of interleukin (IL)-10, a major immunoregulatory cytokine, by phagocytes during clearance of apoptotic cells is critical to ensuring cellular homeostasis and suppression of autoimmunity. Little is known about the regulatory mechanisms in this fundamental process. We report that IL-10 production stimulated by apoptotic cells was regulated at the point of transcription in a manner dependent on p38 mitogen-activated protein kinase, partially on the scavenger receptor CD36, and required cell-cell contact but not phagocytosis. By using a reporter assay, we mapped the apoptotic-cell-response element (ACRE) in the human IL10 promoter and provide biochemical and physiological evidence that ACRE mediates the transcriptional activation of IL10 by pre-B cell leukemia transcription factor-1b and another Hox cofactor Pbx-regulating protein 1 in response to apoptotic cells. This study establishes a role of two developmentally critical factors (Pbx1 and Prep-1) in the regulation of homeostasis in the immune system.
Author List
Chung EY, Liu J, Homma Y, Zhang Y, Brendolan A, Saggese M, Han J, Silverstein R, Selleri L, Ma XAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
CD36 Antigens
DNA
DNA-Binding Proteins
Homeodomain Proteins
Humans
Interleukin-10
Macrophages
Mice
Mice, Inbred C57BL
Phagocytosis
Pre-B-Cell Leukemia Transcription Factor 1
Promoter Regions, Genetic
Proto-Oncogene Proteins
Transcription Factors
Transcription, Genetic
p38 Mitogen-Activated Protein Kinases
