Axonal protection by thioredoxin-1 with inhibition of interleukin-1β in TNF-induced optic nerve degeneration.
Interleukin (IL)-1β, a proinflammatory cytokine, is a key mediator in several acute and chronic neurological diseases. Thioredoxin-1 (TRX1) acts as an antioxidant and plays a protective role in certain neurons. We examined whether exogenous TRX1 exerts axonal protection and affects IL-1β levels in tumor necrosis factor (TNF)-induced optic nerve degeneration in rats. Immunoblot analysis showed that IL-1β was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with recombinant human (rh) TRX1 exerted substantial protective effects against TNF-induced axonal loss. The increase in the IL-1β level in the optic nerve was abolished by rhTRX1. Treatment with rhTRX1 also significantly inhibited increased glial fibrillary acidic protein (GFAP) levels induced by TNF. Immunohistochemical analysis showed substantial colocalization of IL-1β and GFAP in the optic nerve after TNF injection. These results suggest that IL-1β is upregulated in astrocytes in the optic nerve after TNF injection and that exogenous rhTRX1 exerts axonal protection with an inhibitory effect on IL-1β.
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan; Department of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan. Electronic address: kitaoka@marianna-u.ac.jp.
Yasushi
Y
Kitaoka
Division of Ophthalmology, Matsue Red Cross Hospital, Matsue, Shimane, Japan; Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
Masaki
M
Tanito
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Kaori
K
Kojima
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Kana
K
Sase
Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
Sachiko
S
Kaidzu
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Yasunari
Y
Munemasa
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Hitoshi
H
Takagi
Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
Akihiro
A
Ohira
Department of Biological Responses, Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Japan.
Junji
J
Yodoi
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058449:Intravitreal Injections; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage*; D013879:Thioredoxins / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
D053583:Interleukin-1beta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C495697:Txn1 protein, rat; D013879:Thioredoxins
Astrocyte; Interleukin-1β; Optic nerve; Thioredoxin; Tumor necrosis factor