title: Dose-dependent anti-inflammatory and neuroprotective effects of an ανβ3 integrin-binding peptide.
abstract: Previous studies have shown that prevention of leukocyte infiltration by targeting integrins involved in transendothelial migration may suppress the clinical and pathological features of neuroinflammatory disease. This study was designed to investigate the effects of C16, an ανβ3 integrin-binding peptide, in an acute experimental allergic encephalomyelitis (EAE) rat model. Multiple histological and immunohistochemical staining, electron microscopy observation, ELISA assay, Western blot, and magnetic resonance imaging (MRI) were employed to assess the degree of inflammation, axonal loss, neuronal apoptosis, white matter demyelination, and extent of gliosis in the brain and spinal cord of differently treated EAE models. The results showed that C16 treatment could inhibit extensive leukocyte and macrophage accumulation and infiltration and reduce cytokine tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) expression levels. A significantly lower clinical score at the peak time of disease was also demonstrated in the C16 treated group. Moreover, astrogliosis, demyelination, neuronal death, and axonal loss were all alleviated in C16 treated EAE animals, which may be attributed to the improvement of microenvironment. The data suggests that C16 peptide may act as a protective agent by attenuating inflammatory progression and thus affecting the expression of some proinflammatory cytokines during neuroinflammatory disease.
authors.affiliation: Institute of Neuroscience, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Han
authors.affiliation: Institute of Neuroscience, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Hangzhou Red Cross Hospital, Hangzhou 310003, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute of Neuroscience, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Neuroscience, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Henry
authors.initials: H
authors.lastname: Davies
authors.affiliation: Brain Research Center, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
authors.forename: David T W
authors.initials: DT
authors.lastname: Yew
authors.affiliation: Institute of Neuroscience, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Marong
authors.initials: M
authors.lastname: Fang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D039302:Integrin alphaVbeta3; D018696:Neuroprotective Agents