Abstract
BackgroundDifferent species and strains of probiotic bacteria confer distinct immunological responses on immune cells. Lactobacillus rhamnosus GR-1 (GR-1) is a probiotic bacterial strain found in both the intestinal and urogenital tracts, and has immunomodulatory effects on several cell types including macrophages. However, detailed immunological responses and the signaling mechanism involved in the response are largely unknown.ResultsWe examined the production of GR-1-induced cytokines/chemokines and signaling events in macrophages. Among 84 cytokines and chemokines examined, GR-1 discretely induced granulocyte colony-stimulating factor (G-CSF) mRNA at highest levels (>60-fold) without inducing other cytokines such as IL-1α, IL-1β, IL-6 and TNF-α (<5-fold). The toll-like receptor (TLR) 2/6-agonist PAM2CSK4, TLR2/1-agonist PAM3CSK4 and TLR4-agonist lipopolysaccharide induced all of these inflammatory cytokines at high levels (>50-fold). The TLR2 ligand lipoteichoic acid activated all mitogen-activated kinases, Akt and NF-κB; whereas, GR-1 selectively activated extracellular regulated kinases and p38, NF-κB and Akt, but not c-Jun N-terminal kinases (JNKs) in a TLR2-dependent manner. Using specific inhibitors, we demonstrated that lack of JNKs activation by GR-1 caused inefficient production of pro-inflammatory cytokines but not G-CSF production. A secreted heat-labile protein-like molecule, 30–100 kDa in size, induced the preferential production of G-CSF.ConclusionThis study elucidated unique signaling events triggered by GR-1, resulting in selective production of the immunomodulatory cytokine G-CSF in macrophages.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0578-2) contains supplementary material, which is available to authorized users.
Highlights
Different species and strains of probiotic bacteria confer distinct immunological responses on immune cells
We found that a proteinlike factor released by Lactobacillus rhamnosus GR-1 (GR-1) and potently induced the immunomodulatory granulocyte colony-stimulating factor (G-CSF) through activating Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), extracellular regulated protein kinases (ERKs) and Akt, but not Jun N-terminal kinases (JNKs), in a TLR2-dependent manner
Production of G-CSF is the most prominent among 84 cytokines and chemokines examined in GR-1-treated macrophages We previously showed that GR-1 potently induces G-CSF but poorly induces tumor necrosis factor-α (TNF-α) production in macrophages
Summary
Different species and strains of probiotic bacteria confer distinct immunological responses on immune cells. LGG was shown to have anti-inflammatory effects on mouse and human macrophage cell lines [7, 13], and renders beneficial effects on chronic dextran sulfate sodium-induced mouse colitis and pouchitis in human [14, 15]. Two soluble factors from LGG, referred to as p75 and p40, prevent apoptotic cell death of intestinal epithelial cells, through activating the epithelial growth factor receptor [16, 17]. These factors ameliorate dextran sulfate sodium-induced acute colitis, as well as oxazolone and trinitrobenzenesulfonic acid-induced chronic colitis in mice [18]. To date, detailed immune responses and signaling mechanisms elicited by GR-1 remain largely unknown
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