RRC ID 36957
著者 Ibusuki K, Sakiyama T, Kanmura S, Maeda T, Iwashita Y, Nasu Y, Sasaki F, Taguchi H, Hashimoto S, Numata M, Uto H, Tsubouchi H, Ido A.
タイトル Human neutrophil peptides induce interleukin-8 in intestinal epithelial cells through the P2 receptor and ERK1/2 signaling pathways.
ジャーナル Int J Mol Med
Abstract Human neutrophil peptides (HNPs) are antimicrobial peptides produced predominantly by neutrophils. We have previously reported that HNP 1-3 levels are increased in the sera and plasma of patients with active ulcerative colitis. The increased expression of interleukin-8 (IL-8) has also been demonstrated in the colonic mucosa of patients with active ulcerative colitis. HNPs induce IL-8 in lung epithelial cells and monocytes through the P2Y6 signaling pathway. However, the association between HNPs and IL-8 in the intestinal mucosa has not yet been investigated. In the present study, we investigated the effects of HNP-1 on the production of IL-8 by human intestinal epithelial cells and the underlying signaling mechanisms. We observed a significant increase in IL-8 expression in the human colon carcinoma cell line, Caco-2, following treatment with HNP-1. The non-selective P2 receptor antagonists, suramin and pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), significantly blocked the HNP-1-induced expression of IL-8 in the Caco-2 cells. The P2Y6-specific antagonist, MRS2578, led to a significant but partial decrease in IL-8 expression, suggesting that P2 receptors in addition to P2Y6 are involved in the HNP-1-induced production of IL-8 by Caco-2 cells. In agreement with this finding, HNP-1 also significantly increased IL-8 production in the P2Y6-negative human colon cancer cell line, HT-29, and this increase was blocked by treatment with suramin and PPADS. HNP-1 significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) in the HT-29 cells. However, the HNP-1-induced production of IL-8 was suppressed by the ERK1/2 inhibitor, U0126, but not by the p38 MAPK inhibitor, SB203580. In conclusion, our data demonstrate that HNP-1 induces IL-8 production not only through P2Y6, but also through additional P2 receptors via an ERK1/2-dependent mechanism in intestinal epithelial cells.
巻・号 35(6)
ページ 1603-9
公開日 2015-6-1
DOI 10.3892/ijmm.2015.2156
PMID 25816245
MeSH Caco-2 Cells Humans Interleukin-8 / biosynthesis* Intestinal Mucosa / metabolism* Isothiocyanates / pharmacology MAP Kinase Signaling System / drug effects* Mitogen-Activated Protein Kinase 1 / metabolism* Mitogen-Activated Protein Kinase 3 / metabolism* Receptors, Purinergic P2 / metabolism* Thiourea / analogs & derivatives Thiourea / pharmacology alpha-Defensins / pharmacology*
IF 3.098
引用数 11
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)