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// Kyung Eun Kim 1,2 , Sungryung Kim 2 , Sunyoung Park 2 , Younkyung Houh 2 , Yoolhee Yang 3 , Seung Beom Park 4 , Sangyoon Kim 4 , Daejin Kim 5 , Dae Young Hur 5 , Seonghan Kim 5 , Hyun Jeong Park 6,* , Sa Ik Bang 3,* and Daeho Cho 1,2,* 1 Department of Cosmetic Sciences, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul, Republic of Korea 2 Department of Biological Sciences, Sookmyung Women’s University, Chungpa-Dong 2-Ka, Yongsan-ku, Seoul, Republic of Korea 3 Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, Republic of Korea 4 Biotech. Team, Cent’l Res. Inst. Ilyang Pharm. Co., Ltd., Gyeonggi-do, Republic of Korea 5 Department of Anatomy, Inje University College of Medicine, Busan, Republic of Korea 6 Department of Dermatology, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: Daeho Cho, email: // Sa Ik Bang, email: // Hyun Jeong Park, email: // Keywords : erythroid differentiation regulator 1 (Erdr1), rheumatoid arthritis, inflammation, interleukin-18 (IL-18), synovial fibroblast migration, Immunology and Microbiology Section, Immune response, Immunity Received : August 25, 2016 Accepted : October 28, 2016 Published : November 03, 2016 Abstract Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and multiple inflammatory cytokines are involved in RA pathogenesis. Interleukin (IL)-18, in particular, has a significant positive correlation with RA. In this study, we investigated the effect of erythroid differentiation regulator 1 (Erdr1), which is negatively regulated by IL-18, in an animal model of inflammatory arthritis, collagen-induced arthritis (CIA) in DBA/1J mice. Treatment of mice with recombinant (r)Erdr1 significantly suppressed the severity of arthritis, histologic features of arthritic tissue, and serum levels of anti-collagen autoantibodies (IgG, IgG1, IgG2a and IgM) in CIA. In addition, IL-18 expression was reduced in the affected synovium of rErdr1-treated mice. Interestingly, Erdr1 treatment suppressed migration in contrast to the pro-migratory effect of IL-18, indicating the therapeutic effects of Erdr1 on CIA through inhibiting synovial fibroblast migration. In addition, Erdr1 inhibited activation of ERK1/2, a key signaling pathway in migration of various cell types. Taken together, these data show that rErdr1 exerts therapeutic effects on RA by inhibiting synovial fibroblast migration, suggesting that rErdr1 treatment might be an effective therapeutic approach for RA.

Natural Killer (NK) cells are active against Aspergillus fumigatus, which in turn is able to impair the host defense. Unfortunately, little is known on the mutual interaction of NK cells and A. fumigatus. We coincubated human NK cells with A. fumigatus hyphae and assessed the gene expression and protein concentration of selected molecules. We found that A. fumigatus up-regulates the gene expression of pro-inflammatory molecules in NK cells, but inhibited the release of these molecules resulting in intracellular accumulation and limited extracellular availability. A. fumigatus down-regulatedmRNA levels of perforin in NK cells, but increased its intra- and extracellular protein concentration. The gene expression of stress related molecules of A. fumigatus such as heat shock protein hsp90 was up-regulated by human NK cells. Our data characterize for the first time the immunosuppressive effect of A. fumigatus on NK cells and may help to develop new therapeutic antifungal strategies.

// Dong Yang 1 , Xinchuan Zheng 1 , Ning Wang 1 , Shijun Fan 1 , Yongjun Yang 1 , Yongling Lu 1 , Qian Chen 1 , Xin Liu 1 and Jiang Zheng 1 1 Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing, China Correspondence to: Jiang Zheng, email: // Xin Liu, email: // Keywords : lipopolysaccharide, kukoamine B, hepatocytes, asialoglycoprotein receptor, Immunology and Microbiology Section, Immune response, Immunity Received : April 30, 2016 Accepted : August 11, 2016 Published : August 15, 2016 Abstract Free bacterial lipopolysaccharide (LPS) is generally removed from the bloodstream through hepatic uptake via TLR4, the LPS pattern recognition receptor, but mechanisms for internalization and clearance of conjugated LPS are less clear. Kukoamine B (KB) is a novel cationic alkaloid that interferes with LPS binding to TLR4. In this study, KB accelerated blood clearance of LPS. KB also enhanced LPS distribution in the hepatic tissues of C57 BL/6 mice, along with LPS uptake in primary hepatocytes and HepG2 cells. By contrast, KB inhibited LPS internalization in Kupffer and RAW 264.7 cells. Loss of TLR4 did not affect LPS uptake into KB-treated hepatocytes. We also detected selective upregulation of the asialoglycoprotein receptor (ASGPR) upon KB treatment, and ASGPR colocalized with KB in cultured hepatocytes. Molecular docking showed that KB bound to ASGPR in a manner similar to GalNAc, a known ASGPR agonist. GalNAc dose-dependently reduced KB internalization, suggesting it competes with KB for ASGPR binding, and ASGPR knockdown also impaired LPS uptake into hepatocytes. Finally, while KB enhanced LPS uptake, it was protective against LPS-induced inflammation and hepatocyte injury. Our study provides a new mechanism for conjugated LPS hepatic uptake induced by the LPS neutralizer KB and mediated by membrane ASGPR binding.