• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.151-159
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• 2019

Lipoteichoic acid isolated from Lactobacillus plantarum K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of $TNF-{\alpha}$ and interleukin (IL)-6. In addition, pLTA increases the survival rate of mice in a septic shock model. In the current study, we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail, pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However, $TNF-{\alpha}$ production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and $TNF-{\alpha}$ induced by PGE-2 and LPS in PMA-differentiated THP-1 cells were mediated by pLTA, but not by other LTAs isolated from either Staphylococcus aureus (aLTA) or L. sakei (sLTA). Further studies revealed that pLTA-mediated IL-10 inhibition and $TNF-{\alpha}$ induction in PGE-2+LPS-stimulated PMA-differentiated THP-1 cells were mediated by dephosphorylation of p38 and phosphorylation of c-Jun N-terminal kinase (JNK), respectively. Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231), which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells. Taken together, our data suggest that pLTA contributes to inflammatory homeostasis through induction of repressed pro-inflammatory cytokines as well as inhibition of excessive anti-inflammatory cytokines.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.675-682
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• 2022

Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

• Journal of Microbiology and Biotechnology
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• v.24 no.8
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• pp.1133-1142
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• 2014

Interleukin-32 (IL-32) is a cytokine and inducer of various proinflammatory cytokines such as $TNF{\alpha}$, IL-$1{\beta}$, and IL-6 as well as chemokines. There are five splicing variants (${\alpha}$, ${\beta}$, ${\gamma}$, ${\delta}$, and ${\varepsilon}$) and IL-$32{\gamma}$ is the most active isoform. We generated human IL-$32{\gamma}$ transgenic (IL-$32{\gamma}$ TG) mice to express high level of IL-$32{\gamma}$ in various tissues, including immune cells. The pathology of sepsis is based on the systemic inflammatory response that is characterized by upregulating inflammatory cytokines in whole body, particularly in response to gram-negative bacteria. We investigated the role of IL-$32{\gamma}$ in a mouse model of experimental sepsis by using lipopolysaccharides (LPS). We found that IL-$32{\gamma}TG$ mice resisted LPS-induced lethal endotoxemia. IL-$32{\gamma}$ reduced systemic cytokines release after LPS administration but not the local immune response. IL-$32{\gamma}TG$ increased neutrophil influx into the initial foci of the primary injected site, and prolonged local cytokines and chemokines production. These results suggest that neutrophil recruitment in IL-$32{\gamma}TG$ occurred as a result of the local induction of chemokines but not the systemic inflammatory cytokine circulation. Together, our results suggest that IL-$32{\gamma}$ enhances an innate immune response against local infection but inhibits the spread of immune responses, leading to systemic immune disorder.