Purine-Metabolizing Ectoenzymes Control IL-8 Production in Human Colon HT-29 Cells

Bahrami, Fatemeh; Kukulski, Filip; Lecka, Joanna; Tremblay, Alain; Pelletier, Julie; Rockenbach, Liliana; Sévigny, Jean

doi:10.1155/2014/879895

Cited by 16 publications

(20 citation statements)

References 60 publications

(61 reference statements)

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“…In addition, Kukulski et al (2010) showed that nucleotides and P2 receptors were required for IL-8 to induce neutrophil migration. In agreement with the above observations, nucleotide hydrolysis by ectoenzymes controlled IL-8 production in the colonic human cell line HT-29 ( Bahrami et al, 2014 ). In addition to these observations, Ivison et al (2011) demonstrated that ATP regulated the inflammatory response to flagellin via TLR5 activation in immortalized human IEC.…”

Section: Discussionsupporting

confidence: 87%

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P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells

et al. 2018

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In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP-2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y6 receptors. qRT-PCR experiments showed that P2Y6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y6 ligand UDP induced expression and secretion of CXCL10. For the other studies, we took advantage of mice deficient in P2Y6 (P2ry6-/-). Similar expression levels of P2Y1, P2Y2, P2X2, P2X4, and A2A were detected in P2ry6-/- and WT IEC. Agonists of TLR3 (poly(I:C)), TLR4 (LPS), P2Y1, and P2Y2 increased the expression and secretion of CXCL10 more prominently in P2ry6-/- IEC than in WT IEC. CXCL10 expression and secretion induced by poly(I:C) in both P2ry6-/- and WT IEC were inhibited by general P2 antagonists (suramin and Reactive-Blue-2), by apyrase, and by specific antagonists of P2Y1, P2Y2, P2Y6 (only in WT), and P2X4. Neither adenosine nor an A2A antagonist had an effect on CXCL10 expression and secretion. Macrophage chemotaxis was induced by the supernatant of poly(I:C)-treated IEC which was consistent with the level of CXCL10 secreted. Finally, the non-nucleotide agonist FGF2 induced MMP9 mRNA expression also at a higher level in P2ry6-/- IEC than in WT IEC. In conclusion, extracellular nucleotides regulate CXCL10 expression and secretion by IEC. In the absence of P2Y6, these effects are modulated by other P2 receptors also present on IEC. These data suggest that the presence of P2Y6 regulates chemokine secretion and may also regulate IEC homeostasis.

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Section: Discussionsupporting

confidence: 87%

“…RNA extraction, cDNA synthesis, and quantification were performed as described previously with some modifications ( Bahrami et al, 2014 ). Briefly, total RNA from stimulated or unstimulated IEC monolayer was extracted with TRIzol then quantified with a Quant-iT RNA BR Assay Kit and Qubit Fluorometer.…”

Section: Methodsmentioning

confidence: 99%

P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells

et al. 2018

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“…However, the silencing of P2Y 2 had no effect on the induction of IL-8. It has been reported that P2 receptors expressed by HT-29 cells are those for P2Y 1 , P2Y 2 , P2Y 4 and P2Y 11 (24,27,32). The selective P2Y 1 antagonist, MRS2179, did not exert any significant inhibitory effects on the HNP-1induced production of IL-8 by HT-29 cells (data not shown).…”

Section: Discussionmentioning

confidence: 82%

“…HNP-1 significantly increases IL-8 production through P2 receptors in P2Y 6 -negative HT-29 cells. To determine the non-P2Y 6 -mediated mechanisms underlying the HNP-1 induction of IL-8, we used HT-29 cells in the subsequent experiments, since HT-29 cells have no, or very low levels of P2Y 6 mRNA expression (24). Exposure of the HT-29 cells to HNP-1 significantly increased IL-8 mRNA expression in a dose-dependent manner ( Fig.…”

Section: Hnp-1 Upregulates Il-8 Expression Partly Through P2ymentioning

confidence: 98%

Human neutrophil peptides induce interleukin-8 in intestinal epithelial cells through the P2 receptor and ERK1/2 signaling pathways

Ibusuki

Sakiyama

Kanmura

et al. 2015

International Journal of Molecular Medicine

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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.

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“…On the contrary, higher concentrations (1-10 mM) of extracellular ATP or the unhydrolyzed ATP analogue 5′-adenylyimido-diphosphate (AMP-PNP), suppress Caco-2 cell proliferation arresting cells cycling at the S phase by inhibiting PKC, ERK and MAP kinase [ 99 ]. The sustained activation of P2 receptors by ATP may lead to IL-8 secretion from human colorectal epithelial cells and may play an important role in tumor progression as well as in the pathology of IBD [ 100 ].…”

Section: P2y Receptors In Digestive Cancermentioning

confidence: 99%

Important roles of P2Y receptors in the inflammation and cancer of digestive system

Wan

Xie

et al. 2016

Oncotarget

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Purinergic signaling is important for many biological processes in humans. Purinoceptors P2Y are widely distributed in human digestive system and different subtypes of P2Y receptors mediate different physiological functions from metabolism, proliferation, differentiation to apoptosis etc. The P2Y receptors are essential in many gastrointestinal functions and also involve in the occurrence of some digestive diseases. Since different subtypes of P2Y receptors are present on the same cell of digestive organs, varying subtypes of P2Y receptors may have opposite or synergetic functions on the same cell. Recently, growing lines of evidence strongly suggest the involvement of P2Y receptors in the pathogenesis of several digestive diseases. In this review, we will focus on their important roles in the development of digestive inflammation and cancer. We anticipate that as the special subtypes of P2Y receptors are studied in depth, specific modulators for them will have good potentials to become promising new drugs to treat human digestive diseases in the near future.

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Purine-Metabolizing Ectoenzymes Control IL-8 Production in Human Colon HT-29 Cells

Cited by 16 publications

References 60 publications

P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells

P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells

Human neutrophil peptides induce interleukin-8 in intestinal epithelial cells through the P2 receptor and ERK1/2 signaling pathways

Important roles of P2Y receptors in the inflammation and cancer of digestive system

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