title: Lactobacillus paracasei modulates LPS-induced inflammatory cytokine release by monocyte-macrophages via the up-regulation of negative regulators of NF-kappaB signaling in a TLR2-dependent manner.
abstract: The application of the probiotic lactobacillus is suggested in the treatment of some inflammatory diseases of intestines due to its potential ability to attenuate inflammation. However, the mechanism is not completely understood. In PBMCs, Lactobacillus paracasei (L. Paracasei) down-regulated the LPS-induced production of TNF-α and IL-6. Using a macrophage-like differentiated THP-1 cell line induced by PMA, we investigated the effect of L. paracasei on the production of pro-inflammatory cytokines by monocyte-macrophages. Treatment of the differentiated THP-1 cells with L. paracasei either concurrently with or before LPS challenge attenuated the LPS-induced secretion of TNF-α and IL-1β. This effect was due to a decrease in IκB phosphorylation and NF-κB nuclear translocation. Furthermore, treatment of the differentiated THP-1 cells with L. paracasei induced the expression of negative regulators of the NF-κB signaling pathway, including the deubiquitinating enzyme A20, suppressor of cytokine signaling (SOCS) 1, SOCS3, and IL-1 receptor-associated kinase (IRAK) 3. Pretreatment with an IRAK4 inhibitor suppressed the L. paracasei-induced expression of these negative regulators and further increased the LPS-mediated expressions of TNF-α and IL-1β. Moreover, treatment with an antibody against Toll-like receptor (TLR) 2 reversed the effect of L. paracasei on inducing negative regulators and inhibiting TNF-α and IL-1β productions. Our findings suggest that L. paracasei inhibits the production of pro-inflammatory cytokines by monocyte-macrophages via the induction of negative regulators of the NF-κB signaling pathway in a TLR2-IRAK4-dependent manner.
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, China.
authors.forename: Ke-Yi
authors.initials: KY
authors.lastname: Sun
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Xu
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xie
authors.affiliation: Cultech Ltd., Swansea, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Plummer
authors.affiliation: Cultech Ltd., Swansea, UK.
authors.forename: James
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, China.
authors.forename: Xiao Fan
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Department of Immunology, Nanjing Medical University, Nanjing, China. Electronic address: jixiaohui@njmu.edu.cn.
authors.forename: Xiao Hui
authors.initials: XH
authors.lastname: Ji
mesh_terms: D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D000069980:Lacticaseibacillus paracasei / Q000276:immunology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000074084:THP-1 Cells; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha
keywords: Lactobacillus paracasei; NF-κB; Negative regulator; Proinflammatory cytokine; TLR2