• Journal of Ginseng Research
• /
• v.43 no.2
• /
• pp.252-260
• /
• 2019

Background: Increases in the average global temperature cause heat stress-induced disorders by disrupting homeostasis. Excessive heat stress triggers an imbalance in the immune system; thus protection against heat stress is important to maintain immune homeostasis. Korean ginseng (Panax ginseng Meyer) has been used as a herbal medicine and displays beneficial biological properties. Methods: We investigated the protective effects of Korean ginseng extracts (KGEs) against heat stress in a rat model. Following acclimatization for 1 week, rats were housed at room temperature for 2 weeks and then exposed to heat stress ($40^{\circ}C$/2 h/day) for 4 weeks. Rats were treated with three KGEs from the beginning of the second week to the end of the experiment. Results: Heat stress dramatically increased secretion of inflammatory factors, and this was significantly reduced in the KGE-treated groups. Levels of inflammatory factors such as heat shock protein 70, interleukin 6, inducible nitric oxide synthase, and tumor necrosis factor-alpha were increased in the spleen and muscle upon heat stress. KGEs inhibited these increases by down-regulating heat shock protein 70 and the associated nuclear $factor-{\kappa}B$ and mitogen-activated protein kinase signaling pathways. Consequently, KGEs suppressed activation of T-cells and B-cells. Conclusion: KGEs suppress the immune response upon heat stress and decrease the production of inflammatory cytokines in muscle and spleen. We suggest that KGEs protect against heat stress by inhibiting inflammation and maintaining immune homeostasis.

• International Journal of Oral Biology
• /
• v.42 no.3
• /
• pp.85-90
• /
• 2017

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

• The Korean Journal of Food And Nutrition
• /
• v.27 no.1
• /
• pp.99-104
• /
• 2014

Platycodon grandiflorum have been used as a traditional remedy and food source. This study was performed to investigate the immunomodulating effects of Platycodon grandiflorum in mouse, using ex vivo experiments. Six to seven-week old mice were fed ad libitum on a chow diet, and water extract of Platycodon grandiflorum was orally administrated at two different concentractions (50 and 500 mg/kg B.W./day) every other day for four weeks. In ex vivo experiments, the highest proliferation of splenocytes and levels of cytokine (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) production were observed in 500 mg/kg BW/day supplementation group for all three cytokines stimulated by LPS. In conclusion, this study suggests that Platycodon grandiflorum extracts may enhance the immune function by regulating the splenocytes proliferation and cytokine production capacity by activating macrophages in mice.

• IMMUNE NETWORK
• /
• v.8 no.1
• /
• pp.1-6
• /
• 2008

Apoptosis signal-regulating kinase 1 (ASK1), a mitogen- activated protein kinase kinase kinase, plays pivotal roles in stress responses. In addition, ASK1 has emerged as a key regulator of immune responses elicited by pathogen-associated molecular patterns (PAMPs) and endogenous danger signals. Recent studies have demonstrated that reactive oxygen species (ROS)-dependent activation of ASK1 is required for LPS-stimulated cytokine production as well as extracellular ATP-induced apoptosis in immune cells. The mechanism of ROS-dependent regulation of ASK1 activity by thioredoxin and TRAFs has been well characterized. In this review, we focus on the molecular details of the activation of ASK1 and its involvement in innate immunity.

• The Korean Journal of Food And Nutrition
• /
• v.21 no.1
• /
• pp.1-6
• /
• 2008

Job's Tears(Yul-Moo) is a grass crop long-used as a traditional medicine; it is also a nourishing food. There are reports of its anti-inflammatory, stomachic, antiallergic activity, and antispastic effects and Job's Tears has been used in China to treat rheumatism, and neuralgia although its warts, rheumanism remains unclear. Thus, the present study was performed to investigate the in vitro effect of Job's Tears extracts on immune function. Here mouse splenocyte proliferation and cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by peritoneal macrophages cultured with ethanol and water extracts of Job's Tears were examined. splenocytes proliferation increased with Job's Tears water extracts supplement at concentrations investigated The cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by ELISA using a cytokine kit And $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production increased water extracts supplementation. This in vitro study suggests that supplementation with Job's Tears water extracts may enhance immune function by regulating the splenocyte proliferation and enhancing cytokine production of activated macrophages.

• The Korean Journal of Food And Nutrition
• /
• v.21 no.3
• /
• pp.263-268
• /
• 2008

Codonopsis lanceolata has long been used as a seasonal food and as a traditional tonic medicine with anti-inflammatory and anti-oxidation properties. The present study investigated the in vitro effect of Codonopsis lanceolata extracts on immune function in mice. After preparing a single cell suspension splenocyte proliferation was determined by the MTT(3-[4,5-dimethylthiazol-2-y]-2,5-diphenyl terazolium bromide) assay. The cytokines IL-1${\beta}$, IL-6, and TNF-$\alpha$ were not secreted by macrophages stimulated with or without LPS as determined by an ELISA cytokine kit assay. After a 48-hr incubation with the mitogens ConA or LPS there was an increase in splenocytes proliferation and in the production of IL-1${\beta}$, IL-6, and TNF-$\alpha$ in the suspensions supplemented with 50, 100, 250, 500 ${\mu}g/m{\ell}$ Codonopsis lanceolata water extract. The results suggest Codonopsis lanceolata water extract may enhance immune function by regulating splenocyte proliferation and stimulating cytokine production.

• Molecules and Cells
• /
• v.42 no.1
• /
• pp.1-7
• /
• 2019

Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.

• BMB Reports
• /
• v.54 no.1
• /
• pp.2-11
• /
• 2021

Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.

• IMMUNE NETWORK
• /
• v.10 no.1
• /
• pp.26-34
• /
• 2010

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. The family of $Fc{\gamma}$ receptors ($Fc{\gamma}Rs$) has emerged as central regulators for modulating both pro-and anti-inflammatory responses. However, the role of $Fc{\gamma}Rs$ in the development of HP has not been investigated yet. Methods: To explore the functional roles of $Fc{\gamma}Rs$ in HP, $Fc{\gamma}R^{-/-}$ and B6 mice were challenged with Saccharopolyspora rectivirgula (SR) antigen intranasally, and compared these mice in terms of the histological change, infiltrated immune cells in BALF and in vitro immune responses. Results: $Fc{\gamma}R^{-/-}$ mice exhibited attenuation of HP in terms of histological alterations, and reduced numbers of neutrophils and macrophages in and the increased CD4 : CD8 ratio of bronchoalveolar lavage fluid. The lungs of $Fc{\gamma}R^{-/-}$ mice showed high production of Th2 cytokine such as IL-4 and slightly low production of Th1 cytokine, INF-${\gamma}$ compared to those of B6 mice. However, SR-specific adaptive immune responses of $Fc{\gamma}R^{-/-}$ mice were similar to those of B6 mice. Conclusion: These results demonstrate that activating $Fc{\gamma}$ receptors play an important role in activating neutrophils and macrophages in pulmonary inflammation and inducing Th1 differentiation by regulating cytokine expression in SR-induced HP.

• IMMUNE NETWORK
• /
• v.14 no.3
• /
• pp.128-137
• /
• 2014

Respiratory viruses can induce acute respiratory disease. Clinical symptoms and manifestations are dependent on interactions between the virus and host immune system. Dendritic cells (DCs), along with alveolar macrophages, constitute the first line of sentinel cells in the innate immune response against respiratory viral infection. DCs play an essential role in regulating the immune response by bridging innate and adaptive immunity. In the steady state, lung DCs can be subdivided into $CD103^+$ conventional DCs (cDCs), $CD11b^+$ cDCs, and plasmacytoid DCs (pDCs). In the inflammatory state, like a respiratory viral infection, monocyte-derived DCs (moDCs) are recruited to the lung. In inflammatory lung, discrimination between moDCs and $CD11b^+$ DCs in the inflamed lung has been a critical challenge in understanding their role in the antiviral response. In particular, $CD103^+$ cDCs migrate from the intraepithelial base to the draining mediastinal lymph nodes to primarily induce the $CD8^+$ T cell response against the invading virus. Lymphoid $CD8{\alpha}^+$ cDCs, which have a developmental relationship with $CD103^+$ cDCs, also play an important role in viral antigen presentation. Moreover, pDCs have been reported to promote an antiviral response by inducing type I interferon production rather than adaptive immunity. However, the role of these cells in respiratory infections remains unclear. These different DC subsets have functional specialization against respiratory viral infection. Under certain viral infection, contextually controlling the balance of these specialized DC subsets is important for an effective immune response and maintenance of homeostasis.