Immunomodulatory Activity of Lactococcus lactis GCWB1176 in Cyclophosphamide-Induced Immunosuppression Model

Jin, Sun Woo; Lee, Gi Ho; Jang, Min Jung; Hong, Gyeong Eun; Kim, Jae Young; Park, Gi Deok; Jin, Hui; Kim, Hyun Su; Choi, Jae Ho; Choi, Chul Yung; Lee, Su Gwon; Jeong, Hye Gwang; Hwang, Yong Pil

doi:10.3390/microorganisms8081175

Cited by 20 publications

(18 citation statements)

References 32 publications

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“…The phagocytosis assay was performed as previously described [ 35 ]. Peritoneal macrophages of ICR mice were aseptically harvested by peritoneal lavage with 5 mL PBS.…”

Section: Methodsmentioning

confidence: 99%

Immune-Enhancing Effect of Submerged Culture of Ceriporia lacerata Mycelia on Cyclophosphamide-Induced Immunosuppressed Mice and the Underlying Mechanisms in Macrophages

Hwang¹,

Lee

Pham

et al. 2022

IJMS

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The white-rot fungi Ceriporia lacerata is used in bioremediation, such as lignocellulose degradation, in nature. Submerged cultures and extracts of C. lacerata mycelia (CLM) have been reported to contain various active ingredients, including β-glucan and extracellular polysaccharides, and to exert anti-diabetogenic properties in mice and cell lines. However, the immunostimulatory effects have not yet been reported. This study aimed to identify the immunomodulatory effects, and underlying mechanisms thereof, of submerged cultures of CLM using RAW264.7 macrophages and cyclophosphamide (CTX)-induced immunosuppression in mice. Compared to CTX-induced immunosuppressed mice, the spleen and thymus indexes in mice orally administered CLM were significantly increased; body weight loss was alleviated; and natural killer (NK) cytotoxicity, lymphocyte proliferation, and cytokine (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, and interleukin [IL]-2) production were elevated in the serum. In RAW264.7 macrophages, treatment with CLM induced phagocytic activity, increased the production of nitric oxide (NO), and promoted mRNA expression of the immunomodulatory cytokines TNF-α, IFN-γ, IL-1β, IL-6, IL-10, and IL-12. In addition, CLM increased the inducible NO synthase (iNOS) concentration in macrophages, similar to lipopolysaccharide (LPS) stimulation. Mechanistic studies showed that CLM induced the activation of the NF-κB, PI3k/Akt, ERK1/2, and JNK1/2 pathways. Moreover, the phosphorylation of NF-κB and IκB induced by CLM in RAW264.7 cells was suppressed by specific MAPKs and PI3K inhibitors. Further experiments with a TLR4 inhibitor demonstrated that the production of TNF-α, IL-1β, and IL-6 induced by CLM was decreased after TLR4 was blocked. Overall, CLM protected against CTX-induced adverse reactions by enhancing humoral and cellular immune functions, and has potential as an immunomodulatory agent.

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“…The phagocytosis assay was performed as previously described [ 35 ]. Peritoneal macrophages of ICR mice were aseptically harvested by peritoneal lavage with 5 mL PBS.…”

Section: Methodsmentioning

confidence: 99%

Immune-Enhancing Effect of Submerged Culture of Ceriporia lacerata Mycelia on Cyclophosphamide-Induced Immunosuppressed Mice and the Underlying Mechanisms in Macrophages

Hwang¹,

Lee

Pham

et al. 2022

IJMS

Self Cite

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“…As expected, SBT or Stig increased the protein expression levels of HO-1 ( Figure 2 H). LPS as a positive control [ 40 ] also increased the levels of NO, iNOS, and HO-1 ( Figure 2 C–F,H).…”

Section: Resultsmentioning

confidence: 97%

SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

Han

Kim

et al. 2022

Antioxidants

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Immune dysregulation is a risk factor for several diseases, including infectious diseases. Immunostimulatory agents have been used for the treatment of immune dysregulation, but deleterious adverse effects have been reported. The present study aims to establish the anti-oxidant and immunity-enhancing effects of Sambu-Tang (SBT), composed of Panax ginseng and Aconitum carmichaeli, and stigmasterol (Stig), an active compound of SBT. Immune-related factors were analyzed in RAW264.7 macrophage cells, mouse primary splenocytes, and the serum and spleen of cyclophosphamide-induced immunosuppressed mice. Results showed that the production levels of nitric oxide (NO) and expression levels of inducible NO synthase and heme oxygenase-1 were increased following SBT or Stig treatment in RAW264.7 cells. SBT or Stig increased the production levels of G-CSF, IFN-γ, IL-12, IL-2, IL-6, and TNF-α and induced the activation of NF-κB in RAW264.7 cells. SBT or Stig promoted splenic lymphocyte proliferation and increased splenic NK cell cytotoxic activity. In addition, SBT or Stig enhanced the levels of IFN-γ, IL-12, IL-2, IL-6, or TNF-α in the serum and spleen of the immunosuppressed mice. SBT or Stig increased the superoxide dismutase activity in the spleen. Collectively, SBT and Stig possess anti-oxidant and immunomodulatory activities, so they may be considered effective natural compounds for the treatment of various symptoms caused by immune dysregulation.

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“…Oral administration of LAB is reported to ameliorate cyclophosphamide-induced immunosuppression by activating NK cells in mice (50).The antitumoral effect of LAB treatment has also been studied in mouse model. For instance, preventive intranasal treatment of Lactobacillus casei BL23 delayed tumor onset through a mechanism partially associated with NK cell activation and recruitment (51).…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cell Activation by Weissella cibaria JW15 Isolated from Kimchi

Oh¹,

Lee²

2021

jbv

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Natural killer (NK) cells are innate immune cells with the capacity to eliminate virus-infected and cancer cells. Therefore, enhancing NK cell activity remains a promising strategy to control viral infection and cancer development. Recent studies highlighted the immunostimulatory effect of lactic acid bacteria (LAB), especially via activation of NK cells. Among LAB, Weissella cibaria JW15, isolated from kimchi, activated splenocytes and enhanced immune responses, but whether JW15 enhanced NK cell activity was unclear. In this study, we investigated if JW15 affects NK cell activity and a possible role of exopolysaccharides (EPS) produced by JW15 in immune-stimulatory activity. Splenocytes or NK cells isolated from mice were treated with live JW15 or EPS, and then evaluated for cell surface levels of activation markers, intracellular levels of granzyme B and perforin, cytokine production, including IFN-γ, and cytotoxicity against tumor cells. Our results revealed that JW15 induced the activation of NK cells, as shown by increased NK cell cytotoxicity activity, as well as increased activation markers and IFN-γ production. In addition, EPS activated NK cells and splenocytes, leading to the secretion of various cytokines. Furthermore, oral administration of live JW15 increased NK cell cytotoxicity. Taken together, our findings suggest JW15 as a promising probiotic candidate strain with the immune-enhancing potential to prevent or treat viral infection and cancer.

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Immunomodulatory Activity of Lactococcus lactis GCWB1176 in Cyclophosphamide-Induced Immunosuppression Model

Cited by 20 publications

References 32 publications

Immune-Enhancing Effect of Submerged Culture of Ceriporia lacerata Mycelia on Cyclophosphamide-Induced Immunosuppressed Mice and the Underlying Mechanisms in Macrophages

Immune-Enhancing Effect of Submerged Culture of Ceriporia lacerata Mycelia on Cyclophosphamide-Induced Immunosuppressed Mice and the Underlying Mechanisms in Macrophages

SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

Natural Killer Cell Activation by Weissella cibaria JW15 Isolated from Kimchi

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