Brief Article
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World J Gastroenterol. Sep 7, 2013; 19(33): 5500-5507
Published online Sep 7, 2013. doi: 10.3748/wjg.v19.i33.5500
Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1
Atsushi Iraha, Hiroshi Chinen, Akira Hokama, Takumi Yonashiro, Tetsu Kinjo, Kazuto Kishimoto, Manabu Nakamoto, Tetsuo Hirata, Nagisa Kinjo, Futoshi Higa, Masao Tateyama, Fukunori Kinjo, Jiro Fujita
Atsushi Iraha, Akira Hokama, Kazuto Kishimoto, Tetsuo Hirata, Futoshi Higa, Masao Tateyama, Jiro Fujita, Department of Infectious, Respiratory, and Digestive Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
Hiroshi Chinen, Tetsu Kinjo, Manabu Nakamoto, Nagisa Kinjo, Fukunori Kinjo, Department of Endoscopy, University of the Ryukyus Hospital, Okinawa 903-0215, Japan
Takumi Yonashiro, Uruma Bio Co Ltd, Uruma, Okinawa 904-2234, Japan
Author contributions: Iraha A and Chinen H designed and performed the research; Iraha A wrote the manuscript; Hokama A reviewed the manuscript; Yonashiro T, Kinjo T, Kishimoto K, Nakamoto M, Hirata T and Kinjo N provided technical support; Hokama A, Higa F, Tateyama M, Kinjo F and Fujita J supervised the project.
Correspondence to: Akira Hokama, MD, PhD, Assistant Professor, Department of Infectious, Respiratory, and Digestive Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. hokama-a@med.u-ryukyu.ac.jp
Telephone: +81-98-8951144 Fax: +81-98-8951414
Received: April 25, 2013
Revised: July 7, 2013
Accepted: July 23, 2013
Published online: September 7, 2013
Processing time: 136 Days and 11.5 Hours
Abstract

AIM: To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells.

METHODS: In Caco-2 cell monolayer models, the disruption of barrier function by oxidative stress is mediated by H2O2. The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance (TER) and permeability was estimated by measuring the paracellular transport of FITC-labeled 4-kDa dextran (FD4). The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux. The expression of tight junction (TJ) proteins was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining.

RESULTS: Without H2O2 treatment, fucoidan significantly increased the TER compared to control (P < 0.05), indicating a direct enhancement of intestinal epithelial barrier function. Next, H2O2 disrupted the epithelial barrier function in a time-dependent manner. Fucoidan prevented the H2O2-induced destruction in a dose-dependent manner. Fucoidan significantly decreased H2O2-induced FD4 flux (P < 0.01), indicating the prevention of disruption in paracellular permeability. RT-PCR showed that Caco-2 cells endogenously expressed claudin-1 and -2, and occludin and that H2O2 reduced the mRNA expression of these TJ proteins. Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin. Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface. H2O2 disrupted the integrity of claudin-1. Treatment with fucoidan dramatically attenuated the expression of claudin-1.

CONCLUSION: Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1. Thus, fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.

Keywords: Fucoidan; Tight junction; Intestinal epithelial cells; Oxidative stress; Inflammatory bowel diseases

Core tip: The oxidative stress-induced disruption of the intestinal epithelial cells and subsequent increased paracellular permeability are critically important in the pathogenesis of inflammatory bowel diseases (IBD). A growing body of experimental evidence indicates that fucoidan, a dietary substance of fucose-enriched sulfated polysaccharides, display a wide variety of pharmacological anti-inflammatory activities. This study demonstrates that fucoidan protected the epithelial barrier function from oxidative injury of the tight junction as well as barrier disruption by upregulating the expression of claudin-1. Thus, fucoidan may be an appropriate therapy for the treatment of IBD.