title: Lactobacillus rhamnosus GG and Streptococcus thermophilus induce suppressor of cytokine signalling 3 (SOCS3) gene expression directly and indirectly via interleukin-10 in human primary macrophages.
abstract: In the present study we have characterized T helper type 2 (Th2) [interleukin (IL)-10]/Th1 (IL-12) cytokine expression balance in human primary macrophages stimulated with multiple non-pathogenic Gram-positive bacteria used in the food industry and as probiotic substances. Bacteria representing Lactobacillus, Bifidobacterium, Lactococcus, Leuconostoc, Propionibacterium and Streptococcus species induced anti-inflammatory IL-10 production, although quantitative differences between the bacteria were observed. S. thermophilus was able to induce IL-12 production, while the production of IL-12 induced by other bacteria remained at a low level. The highest anti-inflammatory potential was seen with bifidobacteria, as evidenced by high IL-10/IL-12 induction ratios. All studied non-pathogenic bacteria were able to stimulate the expression of suppressor of cytokine signalling (SOCS) 3 that controls the expression of proinflammatory cytokine genes. Lactobacillus and Streptococcus species induced SOCS3 mRNA expression directly in the absence of protein synthesis and indirectly via bacteria-induced IL-10 production, as demonstrated by experiments with cycloheximide (CHX) and anti-IL-10 antibodies, respectively. The mitogen-activated protein kinase (MAPK) p38 signalling pathway played a key role in bacteria-induced SOCS3 gene expression. Enhanced IL-10 production and SOCS3 gene expression induced by live non-pathogenic Lactobacillus and Streptococcus is also likely to contribute to their immunoregulatory effects in vivo.
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare (THL), University of Helsinki, Finland. sinikka.latvala@thl.fiilkka.julkunen@thl.fi
authors.forename: S
authors.initials: S
authors.lastname: Latvala
authors.forename: M
authors.initials: M
authors.lastname: Miettinen
authors.forename: R A
authors.initials: RA
authors.lastname: Kekkonen
authors.forename: R
authors.initials: R
authors.lastname: Korpela
authors.forename: I
authors.initials: I
authors.lastname: Julkunen
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D019936:Probiotics; D013045:Species Specificity; D048249:Streptococcus thermophilus / Q000276:immunology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; D018664:Interleukin-12