Encephalomyelitis Ameliorates Experimental Autoimmune And
The Journal of Immunology Vibsanin B Preferentially Targets HSP90b, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis Bai-Xin Ye,*,1 Xu Deng,†,1 Li-Dong Shao,† Ying Lu,* Run Xiao,* Yi-Jie Liu,* Yi Jin,* Yin-Yin Xie,* Yan Zhao,* Liu-Fei Luo,* Shun Ma,‡ Ming Gao,x Lian-Ru Zhang,‡ Juan He,† Wei-Na Zhang,* Yi Chen,* Cheng-Feng Xia,† Min Deng,{ Ting-Xi Liu,*,{ Qin-Shi Zhao,† Sai-Juan Chen,* and Zhu Chen* Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation- associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz– enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90b. At the molecular level, inacti- vation of HSP90 can mimic vibsanin B’s effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leuko- cyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90b and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases. The Journal of Immunology, 2015, 194: 4489–4497. eukocyte trafficking is a multistep process consisting of moattractant signals, plays an important role in immune cell de- transendothelial and interstitial migration of leukocytes, velopment, immunosurveillance, and effector functions.
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