Anti-inflammatory effect of IL-6 receptor blockade in corneal alkali burn

被引：53

作者：

Sakimoto, Tohru ^{[1
]}

Sugaya, Satoshi ^{[1
]}

Ishimori, Akiko ^{[1
]}

Sawa, Mitsuru ^{[1
]}

机构：

[1] Nihon Univ, Sch Med, Dept Visual Sci, Div Ophthalmol,Itabashi Ku, Tokyo 1738610, Japan

来源：

EXPERIMENTAL EYE RESEARCH | 2012年 / 97卷 / 01期

关键词：

corneal inflammation; interleukin-6 receptor (IL-6R); IL-6; trans-signaling; ENDOTHELIAL GROWTH-FACTOR; SOLUBLE INTERLEUKIN-6 RECEPTOR; ANTIBODY; INFLAMMATION; EXPRESSION; ALPHA; CELLS;

D O I：

10.1016/j.exer.2012.02.015

中图分类号：

R77 [眼科学];

学科分类号：

100212 [眼科学];

摘要：

We investigated the effect of soluble IL-6R (sIL-6R) blockade on corneal inflammation. Topical instillation of either anti-IL-6R antibody (MR16-1) or phosphate buffered saline (PBS) was applied after wounding BALB/c mice corneas with alkali burn. The vascularized area was significantly reduced in the MR16-1 group. The immunoreactivity of phosphorylated STAT3, Gr-1, and F4/80 diminished significantly in the MR16-1 group. Laser capture microdissection resulted in a significant down-regulation of the mRNA expressions of ICAM-1, MCP-1, and VEGF-A in the corneal stroma of the MR16-1 group. Adding a combination of recombinant IL-6 and sIL-6R resulted in a significant increase in the release of VEGF from human corneal fibroblasts. As the infiltration of inflammatory cells, the expression of phosphorylated STAT3, and the expressions of inflammatory-related molecules in the experimental model of corneal inflammation were significantly inhibited by topical instillation of MR16-1, we deduce that IL-6 trans-signaling plays a significant role in ocular surface inflammation and that the blockade of IL-6R contributes to the reduction in corneal inflammation. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：98 / 104

页数：7

共 34 条

[1]

Interleukin-6 induces both cell growth and VEGF production in malignant mesotheliomas [J].

Adachi, Yasuo ;

Aoki, Chieko ;

Yoshio-Hoshino, Naoko ;

Takayama, Koichi ;

Curiel, David T. ;

Nishimoto, Norihiro .

INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (06) :1303-1311

[2]

Amano S, 1998, INVEST OPHTH VIS SCI, V39, P18

[3]

Effect of IL-6 trans-signaling on the pro-remodeling phenotype of airway smooth muscle [J].

Ammit, Alaina J. ;

Moir, Lyn M. ;

Oliver, Brian G. ;

Hughes, J. Margaret ;

Alkhouri, Hatem ;

Ge, Qi ;

Burgess, Janette K. ;

Black, Judith L. ;

Roth, Michael .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2007, 292 (01) :L199-L206

[4]

Wound healing fibroblasts modulate corneal angiogenic privilege: Interplay of basic fibroblast growth factor and matrix metalloproteinases in corneal angiogenesis [J].

Chang, Jin-Hong ;

Han, Kyu Yeon ;

Azar, Dimitri T. .

JAPANESE JOURNAL OF OPHTHALMOLOGY, 2010, 54 (03) :199-205

[5]

VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment [J].

Cursiefen, C ;

Chen, L ;

Borges, LP ;

Jackson, D ;

Cao, JT ;

Radziejewski, C ;

D'Amore, PA ;

Dana, MR ;

Wiegand, SJ ;

Streilein, JW .

JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (07) :1040-1050

[6]

Immunohistochemical localization of vascular endothelial growth factor, transforming growth factor α, and transforming growth factor β1 in human corneas with neovascularization [J].

Cursiefen, C ;

Rummelt, C ;

Küchle, M .

CORNEA, 2000, 19 (04) :526-533

[7]

Stat3 regulates genes common to both wound healing and cancer [J].

Dauer, DJ ;

Ferraro, B ;

Song, LX ;

Yu, B ;

Mora, L ;

Buettner, R ;

Enkemann, S ;

Jove, R ;

Haura, EB .

ONCOGENE, 2005, 24 (21) :3397-3408

[8]

Triamcinolone acetonide inhibits IL-6- and VEGF-induced angiogenesis downstream of the IL-6 and VEGF receptors [J].

Ebrahem, Quteba ;

Minamoto, Atsushi ;

Hoppe, George ;

Anand-Apte, Bela ;

Sears, Jonathan E. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (11) :4935-4941

[9]

Blockade of interleukin-6 signaling suppresses experimental autoimmune uveoretinitis by the inhibition of inflammatory Th17 responses [J].

Hohki, Satoshi ;

Ohguro, Nobuyuki ;

Haruta, Hiroshi ;

Nakai, Kei ;

Terabe, Fumitaka ;

Serada, Satoshi ;

Fujimoto, Minoru ;

Nomura, Shintaro ;

Kawahata, Hirohisa ;

Kishimoto, Tadamitsu ;

Naka, Tetsuji .

EXPERIMENTAL EYE RESEARCH, 2010, 91 (02) :162-170

[10]

Interleukin-6 receptor-mediated activation of signal transducer and activator of transcription-3 (STAT3) promotes choroidal neovascularization [J].

Izumi-Nagai, Kanako ;

Nagai, Norihiro ;

Ozawa, Yoko ;

Mihara, Masahiko ;

Ohsugi, Yoshiyuki ;

Kurihara, Toshihide ;

Koto, Takashi ;

Satofuka, Shingo ;

Inoue, Makoto ;

Tsubota, Kazuo ;

Okano, Hideyuki ;

Oike, Yuichi ;

Ishida, Susumu .

AMERICAN JOURNAL OF PATHOLOGY, 2007, 170 (06) :2149-2158

← 1 2 3 4 →