title: CAF1-knockout mice are more susceptive to lipopolysaccharide-induced acute lung injury.
abstract: The carbon catabolite repressor protein 4 (CCR4)-negative on TATA (NOT) complex includes multiple subunits and is conserved in the eukaryotic cells. The CCR4-NOT complex can regulate gene expression at different levels. Two subunits of the CCR4-NOT complex, CCR4 and CCR4-associated factor 1 (CAF1), possess deadenylase activity. In yeast, the deadenylase activity is mainly provided by the CCR4 subunit; however, the deadenylase activity is provided by both CCR4 and CAF1 in other eukaryotes. A previous study reported that CAF1 but not CCR4 is required for the decay of a reporter mRNA with AU-rich elements. Our previous study showed that CAF1 is involved in the regulation of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression. Both ICAM-1 and IL-8 play crucial roles in acute lung injury. In the present study, we examined the effects of CAF1 deficiency on IL-8 and ICAM-1 expression and acute lung injury in mice. Here we showed that there were no differences between the wild-type and CAF1-knockout mice on phenotypes. The lung histology and protein and mRNA levels of IL-8 and ICAM-1 in unstimulated wild-type mice were comparable to those in unstimulated CAF1-knockout mice. However, lipopolysaccharide stimulation led to more severe lung histological injury and greatly higher IL-8 and ICAM-1 expression in CAF1-knockout mice compared to the wild-type mice. These results, together with our previous study, suggest that CAF1 is involved in the regulation of lipopolysaccharide-stimulated IL-8 and ICAM-1 expression in vivo and affects the progression of acute lung injury.
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of the Clinical Medical School of Nanjing Medical University, Clinical Medical School of Jiangsu University, Lianyungang.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of the Clinical Medical School of Nanjing Medical University, Clinical Medical School of Jiangsu University, Lianyungang.
authors.forename: Jia-Shu
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of the Clinical Medical School of Nanjing Medical University, Clinical Medical School of Jiangsu University, Lianyungang.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Critical Care Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical University, Affiliated Hospital of the Clinical Medical School of Nanjing Medical University, Clinical Medical School of Jiangsu University, Lianyungang.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
keywords: CAF1; ICAM-1; IL-8; acute lung injury; knockout; mice