Neuroprotective effects of interleukin-6 on NMDA-induced rat retinal damage

被引:35
作者
Inomata, Y
Hirata, A
Yonemura, N
Koga, T
Kido, N
Tanihara, H
机构
[1] Kumamoto Univ, Sch Med, Dept Ophthalmol, Kumamoto 8600811, Japan
[2] Kyoto Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Kyoto, Japan
关键词
interleukin-6; soluble interleukin-6 receptor; gp130; N-methyl-D-aspartate; neuroprotection; retina; TUNEL; retrograde labeling; western blotting;
D O I
10.1016/S0006-291X(03)00127-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study shows that interleukin-6 (IL-6) combined with soluble interleukin-6 receptors (sIL-6R) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Eyes pretreated with a combined injection of IL-6 and sIL-6R had NMDA administered into the vitreous cavity. Morphometric analysis and retrograde labeling analysis found that pretreatment with either IL-6 or sIL-6R alone did not bring about any neuroprotective effect. However, pretreatment with a combined administration of IL-6 and sIL-6R induced a significant neuroprotective effect against NMDA-induced retinal damage. Apoptotic changes in the retina were assessed by the TUNEL method. The results indicated that pretreatment with IL-6 combined with sIL-6R prevents NMDA-induced apoptosis. Western blotting studies demonstrated upregulation of gp130 expression in the NMDA-injected retina. Present studies suggest that IL-6 combined with sIL-6R provides a neuroprotective effect on NMDA-induced retinal damage. Published by Elsevier Science (USA).
引用
收藏
页码:226 / 232
页数:7
相关论文
共 41 条
[1]   Ischemia-induced interleukin-6 as a potential endogenous neuroprotective cytokine against NMDA receptor-mediated excitoxicity in the brain [J].
Ali, C ;
Nicole, O ;
Docagne, F ;
Lesne, S ;
MacKenzie, ET ;
Nouvelot, A ;
Buisson, A ;
Vivien, D .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2000, 20 (06) :956-966
[2]   Role of STAT3 and Pl 3-Kinase/Akt in mediating the survival actions of cytokines on sensory neurons [J].
Alonzi, T ;
Middleton, G ;
Wyatt, S ;
Buchman, V ;
Betz, UAK ;
Müller, W ;
Musiani, P ;
Poli, V ;
Davies, AM .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2001, 18 (03) :270-282
[3]  
Carpenter LR, 1999, ADV PROTEIN CHEM, V52, P109
[4]   An investigation into the potential mechanisms underlying the neuroprotective effect of clonidine in the retina [J].
Chao, HM ;
Chidlow, G ;
Melena, J ;
Wood, JPM ;
Osborne, NN .
BRAIN RESEARCH, 2000, 877 (01) :47-57
[5]   Cellular survival: a play in three Akts [J].
Datta, SR ;
Brunet, A ;
Greenberg, ME .
GENES & DEVELOPMENT, 1999, 13 (22) :2905-2927
[6]  
DONNELLY RP, 1993, J IMMUNOL, V151, P5603
[7]   Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: Involvement of STAT3 in anti-apoptosis [J].
Fukada, T ;
Hibi, M ;
Yamanaka, Y ;
TakahashiTezuka, M ;
Fujitani, Y ;
Yamaguchi, T ;
Nakajima, K ;
Hirano, T .
IMMUNITY, 1996, 5 (05) :449-460
[8]   Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema [J].
Funatsu, H ;
Yamashita, H ;
Noma, H ;
Mimura, T ;
Yamashita, T ;
Hori, S .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 2002, 133 (01) :70-77
[9]   IDENTIFICATION OF INTERLEUKIN-6 (IL-6) EXPRESSING NEURONS IN THE CEREBELLUM AND HIPPOCAMPUS OF NORMAL ADULT-RATS [J].
GADIENT, RA ;
OTTEN, U .
NEUROSCIENCE LETTERS, 1994, 182 (02) :243-246
[10]   MOLECULAR-CLONING AND EXPRESSION OF AN IL-6 SIGNAL TRANSDUCER, GP130 [J].
HIBI, M ;
MURAKAMI, M ;
SAITO, M ;
HIRANO, T ;
TAGA, T ;
KISHIMOTO, T .
CELL, 1990, 63 (06) :1149-1157