PMID- 30524427 OWN - NLM STAT- MEDLINE DCOM- 20191002 LR - 20221207 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Suppression of Intestinal Epithelial Cell Chemokine Production by Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0389 Is Mediated by Secreted Bioactive Molecules. PG - 2639 LID - 10.3389/fimmu.2018.02639 [doi] LID - 2639 AB - Host intestinal epithelial cells (IEC) present at the gastrointestinal interface are exposed to pathogenic and non-pathogenic bacteria and their products. Certain probiotic lactic acid bacteria (LAB) have been associated with a range of host-immune modulatory activities including down-regulation of pro-inflammatory gene expression and cytokine production by IEC, with growing evidence suggesting that these bacteria secrete bioactive molecules with immunomodulatory activity. The aim of this study was to determine whether two lactobacilli with immunomodulatory activity [Lactobacillus rhamnosus R0011 (Lr) and Lactobacillus helveticus R0389 (Lh)], produce soluble mediators able to influence IEC responses to Pattern Recognition Receptor (PRR) ligands and pro-inflammatory cytokines [Tumor Necrosis Factor alpha (TNFalpha), Interleukin-1beta (IL-1beta)], signals inducing IEC chemokine production during infection. To this end, the effects of cell-free supernatants (CFS) from Lr and Lh on IEC production of the pro-inflammatory chemokines interleukin (IL)-8 and cytokine-induced neutrophil chemoattractant 1 (CINC-1) induced by a range of host- or pathogen-derived pro-inflammatory stimuli were determined, and the impact on human HT-29 IEC and a primary IEC line (rat IEC-6) was compared. The Lr-CFS and Lh-CFS did not significantly modulate basal IL-8 production from HT-29 IECs or CINC-1 production from IEC-6 cells. However, both Lr-CFS and Lh-CFS significantly down-regulated IL-8 production from HT-29 IECs challenged with varied PRR ligands. Lr-CFS and Lh-CFS had differential effects on PRR-induced CINC-1 production by rat IEC-6 IECs, with no significant down-regulation of CINC-1 observed from IEC-6 IECs cultured with Lh-CFS. Further analysis of the Lr-CFS revealed down-regulation of IL-8 production induced by the pro-inflammatory cytokines IL-1beta and TNFalpha Preliminary characterization of the bioactive constituent(s) of the Lr-CFS indicates that it is resistant to treatment with DNase, RNase, and an acidic protease, but is sensitive to alterations in pH. Taken together, these results indicate that these lactobacilli secrete bioactive molecules of low molecular weight that may modulate host innate immune activity through interactions with IEC. FAU - Jeffrey, Michael P AU - Jeffrey MP AD - Applied Bioscience Graduate Program, University of Ontario Institute of Technology, Oshawa, ON, Canada. FAU - Strap, Janice L AU - Strap JL AD - Applied Bioscience Graduate Program, University of Ontario Institute of Technology, Oshawa, ON, Canada. AD - Faculty of Science, University of Ontario Institute of Technology, Oshawa, ON, Canada. FAU - Jones Taggart, Holly AU - Jones Taggart H AD - Applied Bioscience Graduate Program, University of Ontario Institute of Technology, Oshawa, ON, Canada. AD - Faculty of Health Sciences, University of Ontario Institute of Technology, Oshawa, ON, Canada. FAU - Green-Johnson, Julia M AU - Green-Johnson JM AD - Applied Bioscience Graduate Program, University of Ontario Institute of Technology, Oshawa, ON, Canada. AD - Faculty of Science, University of Ontario Institute of Technology, Oshawa, ON, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181114 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Chemokines) SB - IM MH - Animals MH - Cell Line, Tumor MH - Chemokines/*immunology MH - Epithelial Cells/*immunology/*microbiology MH - Humans MH - Intestinal Mucosa/*immunology/*microbiology MH - Lactobacillus helveticus/*immunology MH - Lacticaseibacillus rhamnosus/*immunology MH - Rats PMC - PMC6262363 OTO - NOTNLM OT - CINC-1 OT - IL-8 OT - Lactobacillus helveticus R0389 OT - Lactobacillus rhamnosus R0011 OT - PRR OT - chemokine OT - secretome EDAT- 2018/12/14 06:00 MHDA- 2019/10/03 06:00 PMCR- 2018/01/01 CRDT- 2018/12/08 06:00 PHST- 2018/07/27 00:00 [received] PHST- 2018/10/26 00:00 [accepted] PHST- 2018/12/08 06:00 [entrez] PHST- 2018/12/14 06:00 [pubmed] PHST- 2019/10/03 06:00 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.02639 [doi] PST - epublish SO - Front Immunol. 2018 Nov 14;9:2639. doi: 10.3389/fimmu.2018.02639. eCollection 2018.