A novel whey tetrapeptide IPAV reduces interleukin-8 production induced by TNF-α in human intestinal Caco-2 cells. (August 2017)

• Record Type: Journal Article
• Authors: Oyama, Machi; Van Hung, Tran; Yoda, Kazutoyo; He, Fang; Suzuki, Takuya
• Is Part Of: Journal of functional foods. Volume 35(2017)
• Page Start: 376
• Page End: 383
• Publication Date: 2017-08
• Subjects: CaSR calcium sensing receptor -- ESI electric spray ionization -- HPLC high-performance liquid chromatography -- IBD inflammatory bowel disease -- IL interleukin -- ERK extracellular signal-regulated kinase -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- JNK c-Jun N-terminal kinase -- NF-κB nuclear factor kappa B -- qRT-PCR quantitative reverse transcription polymerase chain reaction -- SIR selected ion recording -- TFA myeloperoxidase -- MAPK mitogen-activated protein kinase -- TNF tumour necrosis factor -- TNFR tumour necrosis factor receptor -- Syk spleen tyrosine kinase -- UPLC ultra-high performance liquid chromatography -- WPI whey protein isolate; Peptides -- Whey -- Interleukin-8 -- Intestinal cells -- PepT1; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2017.06.001
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: Regulation of intestinal inflammation by whey protein hydrolysate was examined. Whey protein hydrolysate reduces interleukin-8 production induced by TNF-α. A novel whey tetrapeptide IPAV has been identified as the active peptide. IPAV reduces interleukin-8 production and cellular signalling induced by TNF-α. PepT1 activity is required for the IPAV-mediated anti-inflammatory effect. Abstract: In the present study, an anti-inflammatory effect of enzymatic whey protein hydrolysate was examined in human intestinal Caco-2 cells. Stimulation of Caco-2 cells with tumour necrosis factor (TNF)-α induced interleukin (IL)-8 expression through the activation of nuclear factor kappa B p65, spleen tyrosine kinase and mitogen-activated protein kinases pathways. Pre-treatment of cells with whey protein hydrolysate reduced TNF-α-induced IL-8 expression. Mass spectrometry analysis has identified the active tetrapeptide IPAV, which corresponded to amino acids 94–97 of β-lactoglobulin. Pre-treatment of cells with IPAV reduced TNF-α-induced IL-8 expression and the increase in phosphorylation levels of key cellular signalling proteins. Pharmacological inhibition of peptide transporter 1 (PepT1), but not of calcium-sensing receptor, attenuated IPAV-mediated suppression of IL-8 expression. In summary, a novel anti-inflammatory tetrapeptide IPAV, derived from whey protein hydrolysate, reduced IL-8 expression induced by TNF-α. Our results suggest that IPAV, transported by PepT1, can suppress inflammatory signalling in intestinal cells.