Isoleucine, an Essential Amino Acid, Induces the Expression of Human β Defensin 2 through the Activation of the G-Protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia

Youkou Konno, Toshifumi Ashida, Yuhei Inaba, Takahiro Ito, Hiroki Tanabe, Atsuo Maemoto, Tokiyoshi Ayabe, Yusuke Mizukami, Mikihiro Fujiya, Yutaka Kohgo

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
IBD Center, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.
Innate Immunity Laboratory, Department of Cellular Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.

DOI: 10.4236/fns.2012.34077                

Abstract

Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.

Keywords

Isoleucine; Human β-Defensin; G-Protein Coupled Receptor; Extracellular Signal-Regulated Kinases Pathway; Inflammatory Bowel Disease; Crohn’s Disease

Conflicts of Interest

The authors declare no conflicts of interest.

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