• Journal of Pharmacopuncture
• /
• v.22 no.4
• /
• pp.253-259
• /
• 2019

Objectives: It is reported that tumor-associated macrophages (TAMs) contribute to cancer progression by promoting tumor growth and metastasis. The purpose of this study is to investigate the effect of different fractions of Adenophora triphylla var. japonica (AT) on the polarization of macrophages into the M2 phenotype, a major phenotype of TAMs. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AT. The cytotoxicity of AT in RAW264.7 cells was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RAW264.7 cells were polarized into the M2 phenotype by treatment with interleukin (IL)-4 and IL-13. The expression of M2 macrophage marker genes was detected by reverse transcription polymerase chain reaction (RT-PCR). The phosphorylation level of signal transducer and activator of transcription 6 (STAT6) was investigated by western blot analysis. The migration of Lewis lung carcinoma (LLC) cells was examined by transwell migration assay using conditioned media (CM) collected from RAW264.7 cells as a chemoattractant. Results: Among various fractions of AT, the ethyl acetate fraction of AT (EAT) showed the most significant suppressive effect on the mRNA expression of M2 macrophage markers, including arginase-1, interleukin (IL)-10 and mannose receptor C type 1 (MRC-1), up-regulated by treatment of IL-4 and IL-13. In addition, EAT suppressed the phosphorylation of STAT6, a critical regulator of IL-4 and IL-13-induced M2 macrophage polarization. Finally, the increased migration of Lewis lung carcinoma (LLC) cells by CM from M2-polarized RAW264.7 cells was reduced by CM from RAW264.7 cells co-treated with EAT and M2 polarization inducers. Conclusion: We demonstrated that EAT attenuated cancer cell migration through suppression of macrophage polarization toward the M2 phenotype. Additional preclinical or clinical researches are needed to evaluate its regulatory effects on macrophage polarization and anti-cancer activities.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.9
• /
• pp.1379-1386
• /
• 2020

Acne is a chronic skin disease that typically occurs in the teens and twenties, and its symptoms vary according to age, sex, diet, and lifestyle. The condition is characterized by hyperproliferation of keratinocytes in the epidermis, sebum overproduction, excessive growth of Propionibacterium acnes, and P. acnes-induced skin inflammation. Interleukin (IL)-1α and IL-6 are predominant in the inflammatory lesions of acne vulgaris. These cytokines induce an inflammatory reaction in the skin in the presence of pathogens or stresses. Moreover, IL-1α accelerates the production of keratin 16, which is typically expressed in wounded or aberrant skin, leading to abnormalities in architecture and hyperkeratinization. Orobol (3',4',5,7-tetrahydroxyisoflavone) is a metabolite of genistein that inhibited the P. acnes-induced increases in IL-6 and IL-1α levels in human keratinocytes (HaCaTs) more effectively compared with salicylic acid. In addition, orobol decreased the IL-1α and IL-6 mRNA levels and inhibited the phosphorylation of inhibitor of kappa-B kinase, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, and mitogen-activated protein kinase induced by P. acnes. Finally, the expression of Ki67 was decreased by orobol. Thus, orobol ameliorated the inflammation and hyperkeratinization induced by heat-killed P. acnes and thus has potential for use in functional foods and cosmetics.

• Korean Journal of Food Science and Technology
• /
• v.45 no.3
• /
• pp.385-390
• /
• 2013

The effect of tuna extracts on the production of nitric oxide (NO) and cytokines including interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was investigated. All extracts and fractions from tuna significantly reduced NO production induced by lipopolysaccharide (LPS). The acetone+methylene chloride (A+M) extract, n-hexane and 85% aqueous methanol (MeOH) fractions had stronger inhibitory effects among them. The 85% aqueous MeOH fraction at a 10-${\mu}g$ concentration significantly decreased LPS-induced IL-6 and TNF-${\alpha}$ productions at 6 h of incubation. In the case of LPS-induced IFN-${\gamma}$ production, the 85% aqueous MeOH fraction at a 3-${\mu}g$ concentration showed significantly higher levels at 48 h of incubation. These results show that the 85% aqueous MeOH fraction inhibited the production of NO and pro-inflammatory cytokines (IL-6, TNF-${\alpha}$), suggesting that this fraction acts as a potent immunomodulator.

• Journal of Life Science
• /
• v.19 no.2
• /
• pp.264-270
• /
• 2009

We investigated the effect of black soybean and doenjang with black soybean on production of cytokines including interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) compared with yellow soybean and doenjang with yellow soybean. We also determined inhibitory effect of two types of soybeans and doenjang on tumor metastasis produced by colon 26-M3.1 carcinoma cells. The cytokine productions of mouse splenocytes increased by the exposure of lipopolysaccharide (LPS, 1 ${\mu}g$/ml) compared to without treatment of LPS. The LPS-induced IL-2 production was highest in the black soybean methanol extract, while the methanol extract from black soybean doenjang fermented for 2 mo showed the higher levels of IL-2 without LPS (p<0.05). In case of LPS-induced IL-6 production, the methanol extracts from control, yellow soybean, black soybean doenjang fermented for 2 and 7 mo showed higher levels of IL-6 compared to those of black soybean, and yellow soybean doenjang fermented for 2 mo (p<0.05). The methanol extract of black soybean doenjang fermented for 2 mo showed significantly higher levels of TNF-${\alpha}$ in both with and without LPS (p<0.05). In experiment of tumor metastasis, the treatment (1 mg/mouse) of methanol extract from black soybean doenjang fermented for 7 mo inhibited tumor metastasis by 50% and had the highest inhibitory effect among other samples (p<0.05). From these results, doenjang manufactured with black soybean modulated the production of cytokine and showed anticancer effect, suggesting that this effect was increased with increased periods of fermentation.

• Journal of Microbiology and Biotechnology
• /
• v.23 no.2
• /
• pp.156-160
• /
• 2013

Culture supernatants of splenocytes from C57BL/6 mice were exposed to 0.3, 1.0, and 3.0 ${\mu}g/ml$ cordycepin plus 3.0 ${\mu}g/ml$ lipopolysaccharide (LPS) to investigate the effects of cordycepin (3'-deoxyadenosine) on the production of inflammatory cytokines. Coadministration of 3.0 ${\mu}g/ml$ cordycepin with LPS in cultured murine spleen cells significantly diminished expression of the inflammatory cytokines tumor necrosis factor-${\alpha}$ and interleukin-6 (IL-6) in a time-dependent manner. Expression of the inflammatory cytokine IL-17A was substantially downregulated in a timeand concentration-dependent manner at all cordycepin concentrations. These findings suggest that cordycepin downregulates the immediate hypersensitivity reaction stimulated by LPS.

• BMB Reports
• /
• v.35 no.6
• /
• pp.623-628
• /
• 2002

The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

• Bulletin of the Korean Chemical Society
• /
• v.31 no.4
• /
• pp.921-924
• /
• 2010

Blocking of IL-6 has been postulated to be an effective therapy in the pathogenesis of several inflammatory diseases. The current study was performed to examine the potential effects of alkamides isolated from P. longum and P. nigrum on IL-6 induced Stat3 activation and identify the structure-activity relationship of these alkamides in human hepatoma cells. Among 10 alkamides isolated from P. longum and P. nigrum, compounds 6, 7 and 9 were identified as strong inhibitors of IL-6 action, which inhibit IL-6 induced Stat3-dependent luciferase activities. These inhibitory activities were positively influenced by the presence of piperidine moiety.

• Journal of Embryo Transfer
• /
• v.31 no.4
• /
• pp.323-333
• /
• 2016

Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

• Archives of Pharmacal Research
• /
• v.26 no.4
• /
• pp.306-311
• /
• 2003

Soy, high dietary intake for the oriental population, is a main source of isoflavonoids. Sophoricoside (SOP) an isoflavone glycoside was isolated from immature fruits of Sophora japonica (Leguminosae family) and its inhibitory effect on chemical mediators involved in inflammatory response was investigated in this study. SOP inhibited the interleukin (IL)-6 bioactivity with an $IC_{50}$ value of 6.1 $\mu$M whereas it had no effects on IL-1$\beta$ and TNF-a bioactivities. SOP was identified as a selective inhibitor of cyclooxygenase (COX)-2 activity with an $IC_{50}$ value of 4.4 $\mu$ M, but did not show inhibitory effect on the synthesis of COX-2. However, SOP had no effect on the production of reactive oxygen species including superoxide anions and nitric oxide. These results revealed that in vitro anti-inflammatory action of SOP is significantly different from that of genistein known as a phytoestrogen of soy products. This experimental study has documented an importance of dietary soy isoflavonoids as multifunctional agents beneficial to human health, and will help to clarify protective mechanisms of SOP against inflammatory conditions.

• Journal of Microbiology and Biotechnology
• /
• v.16 no.10
• /
• pp.1605-1612
• /
• 2006

Interleukin (IL)-18, a member of the family of IL-l cytokine, is one of the principal inducers of $interferon-{\gamma}(IFN-{\gamma})$ in T lymphocytes and natural killer cells. The objective of the present study was to evaluate the effect of IL-18 on the expression of chemokine IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. IL-18 had very weak direct effect or synergistic effect with IL-12 on the expression of IP-10 mRNA in C57BL/6 mouse peritoneal macrophages. However, IL-18 pretreatment was found to playa cooperative role in the expression of lipopolysaccharide (LPS)-induced IP-10 mRNA. For the expression of LPS-induced IP-10 mRNA, the synergistic effect was detected after 16 h of IL-18 pretreatment prior to LPS stimulation. The expression level of CD14 in cells stimulated with LPS was not changed by IL-18 pretreatment, and the level of $IFN-{\gamma}$ production during IL-18 pretreatment plus LPS stimulation was barely discernible ($0.36{\pm}0.31pg/ml$). Namely, the synergistic effect of IL-18 pretreatment was not related to a change of LPS receptor, CD14 expression, and the production of $IFN-{\gamma}$ by the interaction between IL-18 and LPS. The synergistic effect of IL-18 pretreatment on the expression of LPS-induced IP-10 was related to not NF-kB but AP-1 activation, and associated with the extracellular signal-regulated kinase (ERK) pathway, one of the mitogen-activated protein kinase signaling pathways. These results provide useful information that may elucidate the mechanisms underlying the effect of IL-18 on the expression of IP-10 mRNA.