Identification of novel mediators of NF-κB through genome-wide survey of monocyte adherence-induced genes

Journal of Leukocyte Biology

Sergei S. Makarov¹  Luda Diatchenko¹  Xiangli Li²  Inga Malinina²  Julie Clarke²  Igor Tchivilev²  Sergei Romanov¹ 

[1] Attagene Inc., Research Triangle Park, North Carolina; Comprehensive Center for Inflammatory Disorders, and Thurston Arthritis Center, University of North Carolina at Chapel Hill Attagene Inc., Research Triangle Park, North Carolina; Attagene Inc., Research Triangle Park, North Carolina; Comprehensive Center for Inflammatory Disorders, and Thurston Arthritis Center, University of North Carolina at Chapel Hill Comprehensive Center for Inflammatory Disorders, and Attagene Inc., Research Triangle Park, North Carolina; Comprehensive Center for Inflammatory Disorders, and Thurston Arthritis Center, University of North Carolina at Chapel Hill Thurston Arthritis Center, University of North Carolina at Chapel Hill Attagene Inc., Research Triangle Park, North Carolina; Comprehensive Center for Inflammatory Disorders, and Thurston Arthritis Center, University of North Carolina at Chapel Hill;Comprehensive Center for Inflammatory Disorders, and Thurston Arthritis Center, University of North Carolina at Chapel Hill Comprehensive Center for Inflammatory Disorders, and Comprehensive Center for Inflammatory Disorders, and Thurston Arthritis Center, University of North Carolina at Chapel Hill Thurston Arthritis Center, University of North Carolina at Chapel Hill Comprehensive Center for Inflammatory Disorders, and Thurston Arthritis Center, University of North Carolina at Chapel Hill

关键词: transcription factors;    cell differentiation;    gene regulation;    inflammation;    SSH subtractive hybridization;   

DOI  :  10.1189/jlb.0405211

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The transcription factor nuclear factor (NF)-κB controls the expression of genes involved in inflammation, cell proliferation, apoptosis, and differentiation. Impaired regulation of NF-κB has been associated with many diseases; thus, there is significant interest in therapeutic approaches based on modulation of this transcription factor. NF-κB activity is controlled by numerous signaling molecules, many of which are potentially to be identified. Monocytes are principal effectors of the immune system, and monocyte adherence is the first step leading to their activation and differentiation. Adherence induces activation of NF-κB, resulting in the induction of proinflammatory genes as well as anti-inflammatory genes, which counterbalance and limit the intensity and duration of NF-κB activation. Here, to identify novel mediators of NF-κB signaling, we used the model of monocyte adherence to perform a systematic, genome-wide survey of adherence-induced genes. Having isolated mRNAs from nonadherent and adherent primary human monocytes, we constructed suppressive subtraction hybridization libraries containing cDNAs, which were differentially regulated by adherence. Of 366 identified differentially expressed genes, most were found to be up-regulated by adherence. Having analyzed a subset of these genes, we found that the library was enriched with inhibitors of NF-κB. Three of those (an orphan nuclear receptor NUR77, a guanosine 5′-diphosphate/guanosine 5′-triphosphate exchange factor RABEX5, and a PRK1-associated protein AWP1) were particularly potent inhibitors of NF-κB activation. Thus, the collection of monocyte adherence-regulated genes represents a rich source for the identification of novel components of the machinery that controls NF-κB activation.

【 授权许可】

Unknown