• Mycobiology
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• v.43 no.4
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• pp.450-457
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• 2015

Medicinal mushrooms have been used worldwide to treat cancer and modulate the immune system. Over the last several years, there has been increasing interest in isolating bioactive compounds from medicinal mushrooms and evaluating their health beneficial effects. Fomes fomentarius is used in traditional oriental medicine and is known to possess antioxidant, antiinflammatory, antidiabetic, and antitumor effects. In the present study, we isolated fomentariol from Fomes fomentarius and investigated its anti-inflammatory effect in murine macrophages (RAW264.7 cells) stimulated with lipopolysaccharides. Fomentariol inhibited the production of nitric oxide and intracellular reactive oxygen species triggered by lipopolysaccharides. Interestingly, fomentariol differentially regulated cytokine production triggered by lipopolysaccharides. Fomentariol effectively suppressed the production of interleukin-$1{\beta}$ and interleukin-6 but not tumor necrosis factor-${\alpha}$. The inhibitory effect of fomentariol against nitric oxide, interleukin-$1{\beta}$, and interleukin-6 production was possibly mediated by downregulation of the extracellular signal-regulated kinase signaling pathway. Taken together, our results suggest that fomentariol differentially modulated inflammatory responses triggered by lipopolysaccharides in macrophages and is one of the bioactive compounds that mediate the physiological effects of Fomes fomentarius.

• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.375-382
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• 2021

Biorenovation is a microbial enzyme-based structural modification of component compounds in natural products and synthetic compounds including plant extracts with the potential benefits of improved biological activities compared with its reaction substrates. In this study, we investigated the anti-inflammatory activity of Distylium racemosum leaf extract and D. racemosum leaf biorenovation extract (DLB). As a result, DLB inhibited nitric oxide, prostaglandin E2, and inflammatory cytokines including tumor necrosis factor-α, interleukin-6, interleukin-1β at non-toxic concentrations. In addition, DLB significantly inhibited inducible nitric oxide synthase and cyclooxygenase-2 on LPS-treated RAW 264.7 macrophages. Based on these results, we suggest that the DLB could be used as a potent anti-inflammatory agents. It also suggests that the application of biological evolution has potential usefulness to increase the practical value of natural products.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.519-526
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• 2023

Present study explored immunostimulatory effects of Astragalus membranaceus and Zanthoxylum schinifolium 1:1 (w:w) mixture (AZM-1:1) in Raw264.7 cells, mouse macrophage derived cells. Treatment with 100-400 ㎍/mL of AZM-1:1 in Raw264.7 cells significantly increased nitric oxide production in parallel with inducible nitric oxide synthase mRNA expression without affecting cytotoxicity. In addition, AZM-1:1 dose-dependently increased prostaglandin E₂ production in conditioned medium along with cyclooxygenase-2 mRNA induction. Moreover, AZM-1:1 induces the transcription of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1. Immunoblot analyses revealed that AZM-1:1 significantly increased the phosphorylation of mitogen-activated protein kinases, provoked phosphorylation-mediated degradation of inhibitory-κBα, and phosphorylated p65. Furthermore, treatment with AZM-1:1 promoted phagocytosis of Escherichia coli particle labeled with green fluorescence. Taken together, AZM-1:1 may be a promising nutraceutical for stimulation the innate immune system, including macrophages.

• Microbiology and Biotechnology Letters
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• v.50 no.3
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• pp.354-360
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• 2022

This research was designed to evaluate the possible anti-inflammatory effects of Carex scabrifolia Steud. extract using RAW264.7 cells. The assessments of these effects were based on cell viability assay, mRNA expression levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNFα), and levels of nitric oxide (NO)/prostaglandin E2 (PGE₂) production. Quantitative real-time polymerase chain reaction showed that treatment with C. scabrifolia Steud. extract decreased the mRNA levels of iNOS, COX2, IL-1α, IL-1β, IL-6, and TNFα. Furthermore, from the production levels of PGE₂/NO, it can be inferred that C. scabrifolia Steud. extract exhibited anti-inflammatory properties. These results suggest that C. scabrifolia Steud. extract contains anti-inflammatory compound(s), and consequently, that it may have applications as a potent cosmeceutical material.

• Advances in Traditional Medicine
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• v.6 no.1
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• pp.27-33
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• 2006

The Sasang constitutional medicine classifies the mankind into four constitutional types according to the individual psychological and physical traits. Differences in the Sasang constitutional medicine may be explained by the genetic factors. In order to determine the association of Sasang constitutional classification and interleukin-1 receptor antagonist (IL-1Ra) in genetic susceptibility to ischemic stroke, we classified the four constitutional types in ischemic stroke patients (n = 125) and the healthy control subjects (n = 107), and genotyped for IL-1Ra polymorphism by polymerase chain reaction (PCR) methods. The distribution of the $IL1RN^*1/IL1RN^*2$ genotype in the ischemic stroke patients was significantly different from the healthy controls (OR = 6.09; P =0.0134). And the prevalence of $IL1RN^*1/IL1RN^*2$ genotype was increased in Taeum-in ischemic stroke patients, as compared to Taeum-in healthy controls (OR = 14.71; P = 0.0144). These results suggest that $IL1RN^*1/IL1RN^*2$ genotype in Taeum-in might be associated with the increasing risk for ischemic stroke. Furthermore, this relationship could provide the basis for a new approach in the investigation of the etiology of ischemic stroke.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.115-121
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• 2018

Upon sensing of microbial infections or endogenous danger signals in macrophages, inflammasome signaling plays a significant role in triggering inflammatory responses via producing interleukin (IL)-$1{\beta}$. Recent studies revealed that active caspase-1, a product of the inflammasome complex, causes maturation of inactive pro-IL-$1{\beta}$ into the active form. However, the underlying mechanism by which this leaderless cytokine is secreted into the extracellular space remains to be elucidated. In this study, we demonstrated that prolonged lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected maturation and extracellular release of IL-$1{\beta}$ through a nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)-independent manner. Short-term treatment (less than 6 h) of LPS induced robust production of the IL-$1{\beta}$ precursor form inside cells but did not promote the maturation and secretion of IL-$1{\beta}$ in bone marrow-derived macrophages or peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to a significant release of matured IL-$1{\beta}$ with no robust indication of caspase-1 activation. Intriguingly, this LPS-triggered secretion of IL-$1{\beta}$ was also observed in NLRP3-deficient macrophages. In addition, this unexpected IL-$1{\beta}$ release was only partially impaired by a caspase-1 and NLRP3 inflammasome inhibitor. Collectively, our results propose that prolonged exposure to LPS is able to drive the maturation and secretion of IL-$1{\beta}$ in an NLRP3 inflammasome-independent manner.

• Biomedical Science Letters
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• v.3 no.2
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• pp.139-150
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• 1997

In order to investigate the effect of aging and the $H_2O$$_2$ localization in association with histological, ultrastructural, and cytochemical studies in lung tissue after interleukin-1$\alpha$(IL-1) induced lung injury, an acute lung injury was induced by instillation of IL-1 into the trachea. Both of 4- and 20-months-old male rats, protein contents in IL-1 treated branchoalveolar lavage increased significantly compared to each control rats. Acute lung injury occured by oxidative stress because neutrophils accumulated in vascular lumen and formed the adhesion with endothelial cells. As these cause, tissue proteins were exuded and leukocytes migrated into the alveolar lumen. Neverthless in these lung injury $H_2O$$_2$ localization of IL-1 treated 20 months rats was not different compared to IL-1 treated 4 months rats. After all aging was not a factor to accelate IL-1 induced lung injury. Based on these results, it is suggested that neutrophil infilteration might be an important cause in acute lung injury, and aging is not a factor to change the acute lung injury by oxidative stress.

• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.300-309
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• 2001

Background : Sepsis is a clinical syndrome characterized by a systemic inflammatory and hemodynamic response to severe bacterial infections that involve various mediators. Endothelin (ET)-1, a potent vasoconstrictor is associated with mu1tiple organ failure, and interleukin (IL)-8, a proinflammtory cytokine, plays a major role in neurophil activation. Both have been reported to be useful parameters in the clinical assessment of sepsis. The levels of ET-1 and IL-8 in the blood were measured in patients with sepsis, and the correlation of both parameters and their relationship with the clinical data was assessed. Methods : 19 sepsis patients and 17 controls were studied. Blood samples of the sepsis patients were drawn in day 1, 3, 7, and 14. The APACHE III scores were calculated in concurrent days. The ET-1 and IL-8 levels were measured using immunoassay methods. Results : The ET-1 levels of patients with sepsis were significantly higher than in the controls. In patients with sepsis, non-survivors had higher ET-1 levels than survivors on day 1 and 7, and patients with shock also had higher ET-1 levels than normotensive patients on admission. The ET-1 levels were significantly correlated with the creatinine levels on day 1, 7, and 14. The IL-8 levels showed a significant correlation with the ET-1 levels on day 14. Conclusion : ET-1 was found to be closely related with the clinical outcome, shock, and renal failure, and showed a correlation with IL-8. These mediators can be considered not only to play pathophysiologic roles but also as useful parameters in the clinical assessment of sepsis.

• The Journal of Korean Medicine
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• v.27 no.1 s.65
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• pp.220-228
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• 2006

Objectives : Interleukin-1 (IL-1)${\beta}$ in articular chondrocytes regulates differentiation, apoptosis, and inflammatory responses. It is still controversial, So, we investigated IL- $1{\beta}$ induces chondrocytes dedifferentiation and death. Also, we studied the role of the mitogen-activated protein kinase (MAPK) subtypes on IL-$1{\beta}$-induced dedifferentiation and apoptosis. Methods : To evaluation of dedifferentiation by chemokines of chondrocytes, we assessed such as proteoglycan, collagen, MMP-3 and MMP-13 by RT-PCR analysis. Also, to assess of apoptosis effect by chemokines, we measured annexin V/propidium iodode (PI) and sub G1 cells in chondrocytes by flowcytometric analysis Results : IL-$1{\beta}$ treatment did not affect activation of ERK-1/2, but stimulation of p38 kinase. Inhibition of phospho ERK-1/2 with PD98059 enhanced IL-1b-induced dedifferentiation, and apoptosis up to 13.5%, whereas inhibition of phospho p38 kinase with SB203580 inhibited dedifferentiation, and apoptosis. Conclusions : Our results indicate that SB203580, p38 kinase inhibitor, inhibits IL-$1{\beta}$-induced dedifferentiation, and apoptosis by the inhibition of type II collagen expression and proteoglycan synthesis of rabbit articular chondrocytes.

• Molecules and Cells
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• v.38 no.10
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• pp.886-894
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• 2015

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.