Mass spectrometry based proteomics profiling of human monocytes
PROTEIN & CELL
Authors: Zeng, Yong; Deng, Fei-Yan; Zhu, Wei; Zhang, Lan; He, Hao; Xu, Chao; Tian, Qing; Zhang, Ji-Gang; Zhang, Li-Shu; Hu, Hong-Gang; Deng, Hong-Wen
Abstract
Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datasets. The top 2000 expressed genes from in vitro datasets and 779 genes from in vivo experiments were integrated into this study. Altogether, a total of 2237 unique monocyte-expressed genes were cataloged. Biological functions of these monocyte-expressed genes were annotated and classified via Gene Ontology (GO) analysis. Furthermore, by extracting the overlapped genes from in vivo and in vitro datasets, a core gene list including 541 unique genes was generated. Based on the core gene list, further gene-disease associations, pathway and network analyses were performed. Data analyses based on multiple bioinformatics tools produced a large body of biologically meaningful information, and revealed a number of genes such as SAMHD1, G6PD, GPD2 and ENO1, which have been reported to be related to immune response, blood biology, bone remodeling, and cancer respectively. As a unique resource, this study can serve as a reference map for future in-depth research on monocytes biology and monocyte-involved human diseases.
Mycobacterial infection induces higher interleukin-1 beta and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase
PLOS ONE
Authors: Chao, Wen-Cheng; Yen, Chia-Liang; Hsieh, Cheng-Yuan; Huang, Ya-Fang; Tseng, Yau-Lin; Nigrovic, Peter Andrija; Shieh, Chi-Chang
Abstract
Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1(-/-)) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1(-/-) mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1 beta and neutrophil chemokines in Ncf1(-/-) mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1 beta in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1 beta production. Moreover, we showed that the abundant NE and IL-1 beta were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1 beta with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung.