title: Enhanced LPS-induced peritonitis in mice deficiency of cullin 4B in macrophages.
abstract: Cullin 4B (CUL4B), a member of the cullin protein family, is a scaffold protein of the CUL4B-RING-E3 ligase complex that ubiquitinates intracellular proteins.CUL4B's targets include cell cycle-regulated proteins and DNA replication-related molecules. In this study, we generated myeloid-specific Cul4b-deficient mice (Cul4b(f/y);LysM-Cre(KI/KI)) to investigate the influence of Cul4b deficiency on innate immunity, especially on the function of macrophages. Our results show that an intraperitoneal injection of lipopolysaccharide (LPS) led to a significant decrease in body weights and increased leukocyte infiltrates with increased chemokines in the peritoneal cavity of Cul4b(f/y);LysM-Cre(KI/KI) mice. However, the proinflammatory cytokines, IL-6 and TNF-α did not increase in LPS-injected Cul4b(f/y);LysM-Cre(KI/KI) mice. Furthermore, bone marrow-derived macrophages from Cul4b(f/y);LysM-Cre(KI/KI) mice secreted higher levels of chemokines but lower levels of TNF-α and IL-6 upon LPS stimulation. Of note, increased proliferation of Cul4b-deficient macrophages was also observed. These results show that myeloid-specific Cul4b deficiency worsens LPS-induced peritonitis. In addition, Cul4b deficiency leads to enhanced DNA replication and proliferation, increased production of chemokines but a decreased production of proinflammatory cytokines of macrophages. Our data highlight a new role of cullin family, CUL4B, in the immune system.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: M-H
authors.initials: MH
authors.lastname: Hung
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Y-R
authors.initials: YR
authors.lastname: Jian
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Tsao
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: S-W
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D044842:Cullin Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007118:Immunoassay; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; C524851:Cul4B protein, mouse; D044842:Cullin Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha