Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 28, 2013; 19(8): 1210-1218
Published online Feb 28, 2013. doi: 10.3748/wjg.v19.i8.1210
Inhibition of pacemaker activity in interstitial cells of Cajal by LPS via NF-κB and MAP kinase
Dong Chuan Zuo, Seok Choi, Pawan Kumar Shahi, Man Yoo Kim, Chan Guk Park, Young Dae Kim, Jun Lee, In Yeoup Chang, Insuk So, Jae Yeoul Jun
Dong Chuan Zuo, Seok Choi, Pawan Kumar Shahi, Jae Yeoul Jun, Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, South Korea
Man Yoo Kim, Chan Guk Park, Young Dae Kim, Jun Lee, Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, South Korea
In Yeoup Chang, Department of Anatomy, College of Medicine, Chosun University, Gwangju 501-759, South Korea
Insuk So, Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul 56-1, South Korea
Author contributions: Zuo DC and Choi S contributed equally to this work; Jun JY designed research; Zuo DC, Choi S, Shahi PK, Kim MY, Park CG, Kim YD and Lee J performed research; Jun JY wrote the paper; So I and Chang IY contributed to the experiment analysis.
Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, No. 2012-0001335
Correspondence to: Jae Yeoul Jun, MD, PhD, Professor, Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-dong, Gwangju 501-759, South Korea. jyjun@chosun.ac.kr
Telephone: +82-62-2306412 Fax: +82-62-2324943
Received: November 28, 2012
Revised: January 7, 2013
Accepted: January 18, 2013
Published online: February 28, 2013
Processing time: 93 Days and 2.7 Hours
Abstract

AIM: To investigate lipopolysaccharide (LPS) related signal transduction in interstitial cells of Cajal (ICCs) from mouse small intestine.

METHODS: For this study, primary culture of ICCs was prepared from the small intestine of the mouse. LPS was treated to the cells prior to measurement of the membrane currents by using whole-cell patch clamp technique. Immunocytochemistry was used to examine the expression of the proteins in ICCs.

RESULTS: LPS suppressed the pacemaker currents of ICCs and this could be blocked by AH6809, a prostaglandin E2-EP2 receptor antagonist or NG-Nitro-L-arginine Methyl Ester, an inhibitor of nitric oxide (NO) synthase. Toll-like receptor 4, inducible NO synthase or cyclooxygenase-2 immunoreactivity by specific antibodies was detected on ICCs. Catalase (antioxidant agent) had no action on LPS-induced action in ICCs. LPS actions were blocked by nuclear factor κB (NF-κB) inhibitor, actinomycin D (a gene transcription inhibitor), PD 98059 (a p42/44 mitogen-activated protein kinases inhibitor) or SB 203580 [a p38 mitogen-activated protein kinases (MAPK) inhibitor]. SB 203580 also blocked the prostaglandin E2-induced action on pacemaker currents in ICCs but not NO.

CONCLUSION: LPS inhibit the pacemaker currents in ICCs via prostaglandin E2- and NO-dependent mechanism through toll-like receptor 4 and suggest that MAPK and NF-κB are implicated in these actions.

Keywords: Interstitial cells of Cajal; Lipopolysaccharide; Mitogen-activated protein kinases; Nuclear factor κB; Small intestine