• IMMUNE NETWORK
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• 제21권6호
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• 대한한의학방제학회지
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• 제31권4호
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• pp.253-264
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• 2023

Objectives : Bambusae Caulis in Liquamen (BCL), a traditional herbal medicine, is a distilled product of condensation from the burning of fresh bamboo stems. We previously identified the anti-oxidant capacity of BCL in hepatocytes and suggested that BCL is a promising therapeutic candidate for treating oxidative stress-induced hepatocellular damage. Despite the importance of the role played by Kupffer cells in liver disease, the efficacy of BCL on Kupffer cells is unclear. Therefore, this study aimed to determine whether BCL could suppress LPS-induced inflammation and LPS+ATP-induced inflammasomes in Kupffer cells. Methods : We used ImKCs, a murine immortalized Kupffer cell line to examined whether BCL inhibited LPS-induced inflammation response and oxidave stress. And, we prepared a total of 18 L of BCL, purchased from Bamboo Forest Foods Co., Ltd. (648 Samdari, Damyang-eup, Damyang-gun, Jeollanam-do, Republic of Korea), was concentrated using a decompression concentrator. Result : The LPS-induced release of inflammatory cytokines was abolished by BCL treatment. Also, BCL treatment suppressed the LPS+ATP-induced expression of inflammasome proteins (NLRP3, IL-1, and IL-18), and inhib β ited the release of IL-1 . BCL decreased LPS-or LPS+ATP-induc β ed reactive oxygen species production. In addition, BCL increased nuclear translocation of Nrf2 and the expression of HO-1 in a time-dependent manner. Conclusion : These results suggest the efficacy of BCL with respect to its anti-inflammatory and anti-inflammasome effects mediated by Nrf2 in Kupffer cells.

• 대한임상검사과학회지
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• 제54권3호
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• pp.201-208
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• 2022

Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.

• BMB Reports
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• 제49권5호
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• pp.276-281
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• 2016

Corosolic acid (CA), a triterpenoid compound isolated from Lagerstroemia speciosa L. (Banaba) leaves, exerts anti-inflammatory effects by regulating phosphorylation of interleukin receptor- associated kinase (IRAK)-2 via the NF-κB cascade. However, the protective effect of CA against endotoxic shock has not been reported. LPS (200 ng/mL, 30 min) induced phosphorylation of IRAK-1 and treatment with CA (10 μM) significantly attenuated this effect. In addition, CA also reduced protein levels of NLRP3 and ASC which are the main components of the inflammasome in BMDMs. LPS-induced inflammasome assembly through activation of IRAK-1 was down-regulated by CA challenge. Treatment with Bay11-7082, an inhibitor of IκB-α, had no effect on CA-mediated inhibition of IRAK-1 activation, indicating that CA-mediated attenuation of IRAK-1 phosphorylation was independent of NF-κB signaling. These results demonstrate that CA ameliorates acute inflammation in mouse BMDMs and CA may be useful as a pharmacological agent to prevent acute inflammation.

• Journal of Ginseng Research
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• 제46권4호
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• pp.515-525
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• 2022

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca²⁺]_i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca²⁺]_i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

• Molecules and Cells
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• 제42권1호
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• pp.1-7
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• 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.

• Journal of Ginseng Research
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• 제44권2호
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• pp.267-273
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• 2020

Background: Continuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress. Methods: We investigated the ability of Korean Red Ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model. Results: Heat stress significantly increased gene and protein expression of oxidative stress-related factors such as catalase and SOD2, but treatment with JP5 (Korean Red Ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation. Conclusions: JP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage.

• Journal of Ginseng Research
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• 제47권2호
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• pp.228-236
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• 2023

Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 μM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1β levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.

• 생명과학회지
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• 제33권11호
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• pp.887-896
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• 2023

염증반응(inflammation)은 발병, 진행, 악성 전이를 포함한 암의 진행과정(tumorigenesis)에서 중요한 역할을 수행하기 때문에 암 치료를 위한 전략으로 고려되고 있다. 감태(Ecklonia cava) 열수추출물(AEC)의 항암활성 동안 나타나는 항염증 반응을 연구하기 위하여, 비만세포(mast cells)의 분포, inducible nitric oxide synthase (iNOS)단백질, cyclooxygenase-2 (COX-2)단백질, nuclear factor (NF)-κB단백질, inflammasome 구성 단백질, inflammatory cytokines 발현의 변화는 AEC를 5주간 경구투여한 CT26 대장암을 내포하는 BALB/cKorl syngeneic 마우스에서 분석하였다. AEC를 처리한 후, 고형암의 무게와 조직 절편의 괴사 부위가 vehicle처리그룹에 비하여 감소하였다. 비만세포의 수는 vehicle처리그룹에 비하여 AEC처리그룹에서 증가했지만 COX-2와 iNOS의 발현은 AEC처리그룹에서 감소하였다. 또한, NF-κB, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)과 Caspase-1 (Cas-1)단백질의 발현도 유사한 감소가 관찰되었다. 더불어, tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α)와 interleukin-6 (IL-6)의 mRNA 발현이 vehicle처리그룹에 비하여 AEC처리그룹에서 감소하였다. 이러한 결과는 AEC가 CT26 고형암을 내포하는 BALB/cKorl syngeneic 마우스에서 항암활성은 염증반응과 밀접한 관련이 있음을 제시하고 있다.

• 농업과학연구
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• 제49권1호
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• pp.11-18
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• 2022

A disrupted immune system during pregnancy is involved in pregnancy complications, such as spontaneous abortion, preeclampsia, and recurrent pregnancy loss. This study examined the role of toll-like receptor (TLR) 4 and ASC (apoptosis-associated speck-like protein containing a CARD [c-terminal caspase recruitment domain]) in pregnancy complications using a lipopolysaccharide (LPS)-induced miscarriage mice model. Incidences of miscarriage and embryonic resorption were examined at 9.5 days of pregnancy in wild-type (WT), ASC knockout (KO), and TLR4 KO mice after injecting them with LPS. The fetuses and placenta were obtained after sacrifice at 15.5 days of pregnancy. A significantly lower frequency of fetus absorption was found in TLR4 KO mice, whereas corresponding absorption outcomes were strongly induced in the WT and ASC KO mice upon an LPS injection. As expected, TLR4 KO mice were resistant to LPS-induced abortion. A histological analysis of the miscarried placenta showed increasing levels of the eosin staining of spongiotrophoblast cells without any obvious difference between WT and ASC KO mice. These results suggest that TLR4 KO mice are resistant to LPS, which affects pregnancy persistence, whereas WT and ASC KO mice show high miscarriage rates due to LPS. Moreover, the ASC adaptor is not directly involved in LPS-induced miscarriages, and the NLRP3 inflammasome can be activated by other proteins in the absence of ASC.