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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

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.