ABSTRACT
Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we establish a gut epithelium-microbe-immune microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), with CD4+ naïve T cells circulating underneath the colonic epithelium. Multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines being secreted into both apical and basolateral compartments. In contrast, the absence of APCs does not allow reliable detection of these cytokines. In the presence of APCs, F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, but no significant change on the secreted cytokines. In contrast, integration of CD4+ naïve T cells reverses this effect by decreasing the transcription of TLR1, IFNA1, and indoleamine 2,3-dioxygenase, and increasing the F. prausnitzii-induced secretion of pro-inflammatory cytokines such as IL-8, MCP-1/CCL2, and IL1A. These results highlight the contribution of individual innate immune cells in the regulation of the immune response triggered by the gut commensal F. prausnitzii. The successful integration of defined populations of immune cells in this gut microphysiological system demonstrated the usefulness of the GuMI physiomimetic platform to study microbe-epithelial-immune interactions in health and disease.
ABSTRACT
BACKGROUND: Gumi Bao decoction is effective for the treatment of osteoporosis, but the theoretical and scientific basis is unknown. This study aimed to observe the effect of Gumi Bao decoction on Dickkopf-related protein 1 (DKK1) mRNA, runt-related transcription factor 2 (Runx2) mRNA, and cathepsin K (CTSK) mRNA in glucocorticoid-induced osteoporosis (GIOP) in rats and to investigate the underlying mechanism. METHODS: Sixty Sprague-Dawley (SD) rats were weighed and randomly divided into six groups: the normal control group (NC group), the methylprednisolone group (Met group), the Fosamax group, the low-dose Gumi Bao Decoction group (GBDL group), the medium-dose Gumi Bao Decoction group (GBDM group), and the high-dose Gumi Bao Decoction group (GBDH group). The basic physiological conditions of the rats and the bone morphology of the fourth lumbar vertebra and the left femur of three rats in each group were observed, and the mRNA expressions of bone tissue-related genes were detected. RESULTS: After administration, DKK1 mRNA expression was significantly up-regulated in the Met group compared to the NC group (P<0.001). Meanwhile, DKK1 mRNA was significantly down-regulated in the Fosamax group compared with the Met group (P<0.001). There was a significant difference in the down-regulation of DKK1 mRNA between the GBDM and GBDH groups (P<0.001). Runx2 mRNA was considerably down-regulated in the Met group compared with the NC group (P<0.001). Runx2 mRNA was up-regulated in the GBDM group, and the GBDH group was significantly different compared to the Met group (P<0.001). CTSK mRNA was significantly up-regulated in the Met group compared to the NC group (P<0.001). Compared with the Met group, CTSK mRNA expression was significantly down-regulated in the Fosamax group (P<0.001), as well as in the GBDL, GBDM, and GBDH groups (P<0.001). At 200× and 400×, there were significantly fewer osteoblasts and osteoclasts in the Met group than in the Fosamax, GBDM, and GBDH groups. CONCLUSIONS: The imbalance of bone homeostasis of GIOP is caused by an increase in bone resorption and decreased osteogenesis. Gumi Bao could regulate bone metabolism through the action of DKK1 via the Wnt/ß-catenin signaling pathway, up-regulating Runx2 mRNA and down-regulating CTSK mRNA.
Subject(s)
Glucocorticoids , Osteoporosis , Animals , Methylprednisolone/therapeutic use , Osteoporosis/chemically induced , Osteoporosis/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-DawleyABSTRACT
This study was carried out to characterize the occurrence and concentrations of a variety of volatile organic compounds (VOCs) including aliphatic, aromatic, halogenated, nitrogenous, and carbonyl compounds, in the ambient air of Gumi City, where a large number of electronics industries are found. Two field monitoring campaigns were conducted for a one year period in 2003/2004 and 2010/2011 at several sampling sites in the city, representing industrial, residential and commercial areas. More than 80 individual compounds were determined in this study, and important compounds were then identified according to their abundance, ubiquity and toxicity. The monitoring data revealed toluene, trichloroethylene and acetaldehyde to be the most significant air toxics in the city, and their major sources were mainly industrial activities. On the other hand, there was no clear evidence of an industrial impact on the concentrations of benzene and formaldehyde in the ambient air of the city. Overall, seasonal variations were not as distinct as locational variations in the VOCs concentrations, whereas the within-day variations showed a typical pattern of urban air pollution, i.e., increase in the morning, decrease in the afternoon, and an increase again in the evening. Considerable decreases in the concentrations of VOCs from 2003 to 2011 were observed. The reductions in the ambient concentrations were confirmed further by the Korean PRTR data in industrial emissions within the city. Significant decreases in the concentrations of benzene and acetaldehyde were also noted, whereas formaldehyde appeared to be almost constant between the both campaigns. The decreased trends in the ambient levels were attributed not only to the stricter regulations for VOCs in Korea, but also to the voluntary agreement of major companies to reduce the use of organic solvents. In addition, a site planning project for an eco-friendly industrial complex is believed to play a contributory role in improving the air quality of the city.
Subject(s)
Air Pollutants/analysis , Cities , Industry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/toxicity , Geography , Republic of Korea , Seasons , Time FactorsABSTRACT
OBJECTIVES: The aim of the present study was to determine the prevalence of osteopenia and osteoporosis in women aged 20 years and older in Gumi province. METHODS: We recruited a total of 2,347 women aged 20 years and older in Gumi province who visited the health care center in Soonchunhyang University Gumi hospital from January 2010 to December 2011. The bone mineral densities in the calcaneus were measured by an ultrasound bone densitometry. Osteoporosis and osteopenia were defined by World Health Organization criteria. Age-specific prevalence of osteoporosis and osteopenia in Gumi province were determined and compared with the prevalence of osteoporosis and osteopenia from other provinces within Korea. The prevalence of each was described by %. RESULTS: Age-specific prevalence of osteoporosis was less than 2% in women younger than 50 years but it rapidly increased in those older than 55 years and up to about 50% in women older than 70 years. The prevalence of osteoporosis in women in Gumi province was lower than that of Kangwon province. However, its results were higher than Jung-up province. In addition, the prevalence of osteoporosis in women in Gumi province was lower than other provinces including: Gang-hwa, Chun-cheon, Chung-ju, Jungnang and Gangseo in Seoul, Korea Health Statistics 2009. CONCLUSION: The age-specific prevalence of osteoporosis in women in Gumi province increased with ages, especially in those older than 55 years. Also, the prevalence of osteoporosis in women in Gumi province was lower than Kangwon and other provinces within Korea as stated by Korea Health Statistics 2009. However, its results were higher than Jung-up province.