title: The probiotic mixture VSL#3 dampens LPS-induced chemokine expression in human dendritic cells by inhibition of STAT-1 phosphorylation.
abstract: VSL#3, a mixture of 8 different probiotic bacteria, has successfully been used in the clinic to treat Ulcerative Colitis. We previously identified the modulation of chemokines as a major mechanism in the protective effect of the VSL#3 in a mouse model of colitis. This was supported by in vitro studies that implicated a role for VSL#3 in the suppression of LPS-induced chemokine production by mouse bone marrow-derived dendritic cells (DC). Herein, we validated these findings employing human monocyte-derived DC. Stimulation of human DC with LPS, VSL#3, or a combination of both resulted in their maturation, evident from enhanced expression of activation markers on the cell-surface, as well as the induction of various chemokines and cytokines. Interestingly, a set of LPS-induced chemokines was identified that were suppressed by VSL#3. These included CXCL9, CXCL10, CCL2, CCL7, and CCL8. In silico approaches identified STAT-1 as a dominant regulator of these chemokines, and this was confirmed by demonstrating that LPS-induced phosphorylation of this transcription factor was inhibited by VSL#3. This indicates that VSL#3 may contribute to the control of inflammation by selective suppression of STAT-1 induced chemokines.
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands; Department of Immunohematology and Bloodtransfusion, Leiden University Medical Centrum, Leiden, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Mariman
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Tielen
authors.affiliation: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Centrum, Leiden, The Netherlands.
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands.
authors.forename: Lex
authors.initials: L
authors.lastname: Nagelkerken
mesh_terms: D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D010766:Phosphorylation; D019936:Probiotics / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human