C-X-C motif chemokine receptor 3 (CXCR3) is a G protein-coupled receptor for three ligands which are C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 [1]. Previously we have reported that CXCL10 promotes pro-inflammatory cytokine expression, and forms positive feedback loop [2], [3]. In the present study, we described mRNA expression of CXCL9 and CXCL11 under CXCL10 stimuli in the presence or absence of CXCR3 antagonist, JN-2 in bone marrow-derived macrophages (BMMs) and CD4⁺ T cells. In addition, we examined pro-inflammatory cytokine expression under CXCL9 or CXCL11 stimuli in BMMs and CD4⁺ T cells.

01 Mar 2018·European Journal of Pharmacology

JN-2, a C-X-C motif chemokine receptor 3 antagonist, ameliorates arthritis progression in an animal model

Article

Author: Lee, Zang Hee ; Lee, Jong-Ho ; Kim, Bongjun ; Ha, Hyunil ; Kim, Hong-Hee ; Jin, Won Jong

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by uncontrolled joint inflammation and destruction of bone and cartilage. Previous studies have shown that C-X-C motif chemokine 10 (CXCL10) has important roles in RA development and that blocking CXCL10 expression effectively inhibits arthritis progression in animal models. However, clinical study using anti-CXCL10 monoclonal antibody (MDX-1100) to block CXCL10 expression in patients with RA did not show significant effectiveness. Therefore, we turned our attention to C-X-C motif chemokine receptor 3 (CXCR3), which is a receptor for CXCL9, CXCL10, and CXCL11, to treat RA. In the present study, administration of JN-2, our newly developed CXCR3 antagonist, ameliorated the progression of arthritis in a collagen-induced arthritis animal model. JN-2 also inhibited CXCR3-induced cell migration and pro-inflammatory cytokine expression of bone marrow-derived macrophages and CD4⁺ T cells in vitro. In addition, we found that CXCL10 formed an auto-amplification loop through activation of NFκB. Furthermore, Phosphorylation of p65 at serine 536 played an important role in the auto-amplification of CXCL10. Overall, the present results demonstrated that JN-2 decreased inflammation by inhibiting CXCR3-enhanced cell migration and pro-inflammatory cytokine expression, which then ameliorated arthritis progression.

Frontiers in MicrobiologyQ2 · BIOLOGY

Liquor Flavour Is Associated With the Physicochemical Property and Microbial Diversity of Fermented Grains in Waxy and Non-waxy Sorghum (Sorghum bicolor) During Fermentation

Q2 · BIOLOGY

ArticleOA

Author: Huang, Ting ; Feng, Baili ; Gong, Xiangwei ; Yan, Zongke ; Liu, Lili ; Soe Htet, Maw Ni ; Deng, Xiping ; Liu, Chunjuan ; Zhai, Qinghua ; Jia, Zhiyong ; Zhao, Guan

The fermentation process of Chinese Xifeng liquor involves numerous microbes. However, the sources of microbes in fermented grain and the link between liquor flavour and physicochemical properties and microbial diversity during fermentation still remain unknown. Herein, two waxy (JiNiang 2 [JN-2] and JinNuo 3 [JN-3]) and four non-waxy (JiZa 127 [JZ-127], JinZa 34 [JZ-34], LiaoZa 19 [LZ-19], and JiaXian [JX]) sorghum varieties were selected for the comprehensive analysis of the relationship between liquor flavour and the physicochemical properties and microbial diversity of fermented grains. Results showed that ethyl acetate was the main flavour component of JZ-127, JZ-34, and JX, whereas ethyl lactate was mainly detected in JN-2, JN-3, and LZ-19. Ethyl lactate accounted for half of the ethyl acetate content, and JX exhibited a higher liquor yield than the other sorghum varieties. The fermented grains of waxy sorghum presented higher temperature and reducing sugar contents but lower moisture and starch contents than their non-waxy counterparts during fermentation. We selected JN-3 and JX sorghum varieties to further investigate the microbial changes in the fermented grains. The bacterial diversity gradually reduced, whereas the fungal diversity showed nearly no change in either JN-3 or JX.Lactobacilluswas the most abundant bacterial genus, and its level rapidly increased during fermentation. The abundance ofLactobacillusaccounted for the total proportion of bacteria in JX, and it was higher than that in JN-3.Saccharomyceswas the most abundant fungal genus in JX, but its abundance accounted for a small proportion of fungi in JN-3. Four esters and five alcohols were significantly positively related to Proteobacteria, Bacteroidetes, and Actinobacteria; Alphaproteobacteria, Actinobacteria, and Bacteroidia; Bacillales, Bacteroidales, and Rhodospirillales; andAcetobacter,Pediococcus, andPrevotella_7. This positive relation is in contrast with that observed for Firmicutes, Bacilli, Lactobacillales, andLactobacillus. Meanwhile,Aspergilluswas the only fungal microorganism that showed a significantly negative relation with such compounds (except for butanol and isopentanol). These findings will help in understanding the fermentation mechanism and flavour formation of fermented Xifeng liquor.

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Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Preclinical	KR	Seoul National University	-

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