• Archives of Pharmacal Research
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• v.26 no.11
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• pp.960-966
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• 2003

Macrophages play an important role in host defenses by killing tumors and virus infections and producing secretory products. High mannuronic acid (HMA) containing alginate was examined to determine the mechanisms by which HMA-activated macrophages resist infection with HSV-1 and inhibit the growth of tumor cells. The ability of macro phages to resist infection with HSV-1 or to inhibit the growth of tumor cells was assessed following treatment with HMA alginate in the presence of either antibodies to various cytokines or inhibitors/scavengers of toxic macrophage products. Only antibodies to IFN-$\alpha$/$\beta$ were able to abrogate the protective effects of HMA alginate in macrophages infected with HSV-1, suggesting that the antiviral activity induced by this immunomodulator was mediated by the production of IFN-$\beta$. In contrast, anti-TNF-$\alpha$, anti-IFN and inhibitors of nitric oxide and reactive oxygen species were all able to partially abrogate HMA-induced cytostatic activity, suggesting that multiple mechanisms are involved in macrophage cytostasis. These results indicate that the HMA-induced intrinsic antiviral and extrinsic cytotoxic activites are mediated by different mechanisms.

• Development and Reproduction
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• v.21 no.1
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• pp.93-100
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• 2017

Obesity is characterized by a state of chronic low-grade inflammation and insulin resistance, which are aggravated by the interaction between hypertrophic adipocytes and macrophages. In this study, we investigated the effects of tangeretin on inflammatory changes and glucose uptake in a coculture of hypertrophic adipocytes and macrophages. Tangeretin decreased nitric oxide production and the expression of interleukin (IL)-6, $IL-1{\beta}$, tumor necrosis $factor-{\alpha}$, inducible nitric oxide synthase, and cyclooxygenase-2 in a coculture of 3T3-L1 adipocytes and RAW 264.7 cells. Tangeretin also increased glucose uptake in the coculture system, but did not affect the phosphorylation of insulin receptor substrate (IRS) and Akt. These results suggest that tangeretin improves insulin resistance by attenuating obesity-induced inflammation in adipose tissue.

• Natural Product Sciences
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• v.15 no.2
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• pp.83-89
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• 2009

Polygoni multiflori Ramulus (PM), the stem of Polygonum multiflorum Thunb. has been widely used as a traditional medicine for the treatment of lots of diseases. In macrophages, nitric oxide is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions in inflammation. In the present study, it was investigated that the inhibitory effects on NO and proinflammatory cytokines such as tumor necrosis factor alpha (TNF-${\alpha}$), interleukin-6 (IL-6) and the mechanism of down-regulation of immune response by 85% methanol extracts of PM in mouse (C57BL/6) peritoneal macrophages. Extracts of PM (0.1, 1 mg/ml) suppressed NO production and showed inhibition of proinflammatory cytokines like TNF-${\alpha}$, IL-6 and it attenuated iNOS and COX-2 expression via down-regulation of NF-${\kappa}$B activation. The present results indicate that the 85% methanol extracts of PM has an inhibitory effect on the production of NO through down-regulation of iNOS expression in LPS stimulated mouse peritoneal macrophages and therefore may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.

• Preventive Nutrition and Food Science
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• v.11 no.4
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• pp.273-277
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• 2006

Recently, Rhei Rhizoma extracts (RRE) have begun to receive more attention as potential biological response modifiers. In the present study, we studied the antiproliferative effect of RRE on tumor cells and the effect of RRE on macrophage function. A variety of tumor cells and macrophages were treated with RRE at various concentrations. The effect of RRE on cell proliferation was measured by MTT assay and the effect of RRE on the production of nitric oxide (NO) was determined in the macrophage-like cell lines Raw264.7, C6 and peritoneal macrophages (pMQ). RRE inhibited the growth of tumor cells (e.g., B16, HOS). However, the effects of RRE on the production of NO varied with macrophage types. RRE had no effect on C6 cell growth and slightly increased the growth of Raw264.7 cells. In addition, treatment of normal pMQ with RRE enhanced NO production in a concentration-dependent manner, whereas RRE suppressed NO production at $50\;{\mu}g/mL$ in both Raw264.7 and C6 cells. However, RRE suppressed NO production in LPS/IFN-$\gamma$-stimulated C6 cells. Overall, these results suggest that RRE elicits an antiproliferative property and differentially modulates NO production in various macrophages, and have a potential for therapeutic application.

• Herbal Formula Science
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• v.16 no.2
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• pp.101-114
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• 2008

Objective : The purpose of this study was to investigate the anti-inflammatory effects of Hwagae-san extract(HGSE) on the peritoneal macrophage. Methods : To evaluate anti-inflammatory effects of HGSE, We measured cytokines(interleukin-6; IL-6, interleukin-12; IL-12, tumor necrosis factor-${\alpha}$; TNF-${\alpha}$) and nitric oxide(NO) production in lipopolysaccharide(LPS)-induced macrophages. Furthermore, We examined molecular mechanism using western blot and also LPS-induced endotoxin shock. Results : 1. HGSE did not have any cytotoxic effect in the peritoneal macrophages. 2. HGSE reduced LPS-induced IL-6, TNF-${\alpha}$, IL-12 and NO production in peritoneal macrophages. 3. HGSE inhibited the activation of extracelluar signal-regulated kinase(ERK), C-Jun NH2-terminal kinase(JNK) but not of p38, degradation of IkB-${\alpha}$ in the LPS-stimulated peritoneal macrophages. 4. HGSE inhibited the production of TNF-$\alpha$, IL-6 and IL-12 in serum after LPS injection. Conclusion : These results suggest that HGSE may inhibit the production of TNF-${\alpha}$, IL-6, and IL-12 through inhibition of ERK and JNK activation, and that HGSE may be beneficial for inflammatory diseases.

• Natural Product Sciences
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• v.12 no.2
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• pp.113-117
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• 2006

Quercitrin gallate was previously isolated from Persicaria lapathifolia (Polygonaceae) as an inhibitor of superoxide production. In the present study, quercitrin gallate was found to inhibit interleukin (IL)-6 production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an $IC_{50}$ value of $63\;{\mu}M$. Furthermore, quercitrin gallate attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6 promoter activity, indicating that the compound could down-regulate IL-6 expression at the transcription level. Since nuclear factor (NF)-kB has been shown to play a key role in LPS-inducible IL-6 expression, an effect of quercitrin gallate on LPS-induced NF-kB activation was further analyzed. Quercitrin gallate exhibited a dosedependent inhibitory effect on LPS-induced nuclear translocation of NF-kB without affecting inhibitory kB (IkB) degradation, and subsequently inhibited LPS-induced NF-kB transcriptional activity in macrophages RAW 264.7. Taken together, quercitrin gallate down-regulated LPS-induced IL-6 expression by inhibiting NF-kB activation, which could provide a pharmacological potential of the compound in IL-6-related immune and inflammatory diseases.

• Natural Product Sciences
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• v.2 no.1
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• pp.48-55
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• 1996

The CINC-1 is a member of rat interleukin-8 with chemotactic and activating properties to neutrophils. The CINC-1 induction in LPS-stimulated rat peritoneal macrophages was analyzed using a sensitive enzyme-linked immunosorbent assay. The peritoneal macrophages contained about 3 ng/ml as a basal level, and induced to maximal 18 ng/ml of CINC-1 by stimulation with 5 ${\mu}g/ml$ of LPS. Antiinflammatory steroids of dexamethasone and triamcinolon significantly suppressed the CINC-1 induction, where as aspirin and idomethacin did not show suppression. Inhibitory effects on the CINC-1 induction by natural triterpenoids having steroidal structures were analyzed. Among the 39 kinds of triterpenoids isolated from herbal medicines, acacigenin B and nigaichigoside F1 exhibited the highest suppression on the CINC-1 induction.

• Parasites, Hosts and Diseases
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• v.44 no.1 s.137
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• pp.35-41
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• 2006

Protozoan parasites of the genus Leishmania cause a number of important human diseases. One of the key determinants of parasite infectivity and survival is the surface glycoconjugate lipophosphoglycan (LPG). In addition, LPG is shown to be useful as a transmission blocking vaccine. Since culture supernatant of parasite promastigotes is a good source of LPG, we made attempts to characterize functions of the culture supernatant, and membrane LPG isolated from metacyclic promastigotes of Leishmania major. The purification scheme included anion-exchange chromatography, hydrophobic interaction chromatography and cold methanol precipitation. The purity of supernatant LPG (sLPG) and membrane LPG (mLPG) was determined by SOS-PAGE and thin layer chromatography. The effect of mLPG and sLPG on nitric oxide (NO) production by murine macrophages cell line (J77 4.1 A) was studied. Both sLPG and mLPG induced NO production in a dose dependent manner but sLPG induced significantly higher amount of NO than mLPG. Our results show that sLPG is able to promote NO production by murine macrophages.

• Applied Microscopy
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• v.25 no.1
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• pp.30-47
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• 1995

The ultrastructural changes of adrenal chromaffin cells and ganglion cells in the adrenal gland of vacor-induced diabetic Mongolian gerbils were studied by electron microscopy. After one month of vacor-induced diabetes, some chromaffin cells were filled with dense bodies and large cytosomes with formy contents. Most of degenerating axon terminals were observed on chromaffin cells. A few macrophages were found among chromaffin cells at one month after induction. Several of these macrophages were filled with numerous phagosomes. After one month of vacor-induced diabetes, the ganglion cells showed increase in numbers of dense bodies and degenerating dendrites compared with the normal ganglion cells. Both electron dense and lucent types of degenerating axon terminals were found in interstitial space of the ganglion cells. Degenerating unmyelinated and myelinted axons contained dense and lamellar bodies. The satellite cells and macrophages with engulfed degenerated axon terminals were observed. After three months of vacor-induced diabetes, the unmyelinated and myelinated axons showed degenerative changes, whereas no structural changes could be demonstrated in adrenal ganglion and chromaffin cells. The satellite cells and macrophages containing partially digested debris were still commonly observed in the interstitial space of adrenal medulla. These results suggest that the degenerative changes occur in the adrenal ganglion cells as well as adrenal chromaffin cells of vacor-induced diabetic Mongolian gerbils.

• Tuberculosis and Respiratory Diseases
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• v.65 no.4
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• pp.343-350
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• 2008

PD-L1 is expressed in a variety of antigen-presenting cells and provides T cell tolerance via ligation with its receptor PD-1 and B7-1 on T cells. Stimulation with lipopolysaccharide (LPS) can increase the level of PD-L1 expression in B cells and macrophages, which suggests that this molecule plays a role in the immunosuppression observed in severe sepsis. The aim of this study was to identify which of the downstream pathways of TLR4 are involved in the up-regulation of PD-L1 by LPS in macrophages. Flow cytometry was used to examine the expression of PD-L1 in RAW 264.7 macrophages stimulated with LPS. The following chemical inhibitors were used to evaluate the role of each pathway: LY294002 for PI3K/Akt, SB202190 for p38 MAPK, and U0126 for MEK. LPS induced the expression of PD-L1 in a time- and dose-dependent manner. Transfection of siRNA for TLR4 suppressed the induction of PD-L1. Pretreatment with LY294002 and SB202190 decreased the level of PD-L1 expression but U0126 did not. Overall, the PI3K/Akt and p38 MAPK pathways are involved in the up-regulation of PD-L1 expression in RAW 264.7 macrophages stimulated with LPS.