• Journal of Acupuncture Research
• /
• v.24 no.4
• /
• pp.167-181
• /
• 2007

Objectives: To evaluate expression of MIF mRNA, MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT-3, $NF-{\kappa}B$ p65, COX-2 and iNOS, MMP-9mRNA after injecting deer antler herbal acupuncture solution in a LPS rat model. Methods: The experiment was divided in category of the control group, RA group, and NA group. RA was induced in the mice via injecting 300ug/kg LPS. The deer antler herbal acupuncture solution 50ug/kg was applied on $ST_{35}$(犢鼻) and EX-LE201(內膝眼) for 19days from $3^{rd}$ day of RA inducement. Results: 1. In the deer antler herbal acupuncture solution treated RAW 264.7cell, the mRNA expression of cytokines, RA related inflammation factors, such as the MIF, COX- 2, iNOS, and MMP-g reduced concentration dependently. 2. In the deer antler herbal acupuncture treated mice's synovial membrane, decrease in the cell replication of synovial joint cells, regeneration of blood vessel, fibrosis and fibroblastic cells expansion were observed. 3. Positive reaction of RA-related cytokines MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT3, COX-2, iNOS, $NF-\;{\kappa}B$ p65, MMP-9 was reduced. Conclusion : On the basis of the results, it was concluded that deer antler herbal acupuncture extract has significant protecting ability against acute progressive RA by inhibiting the production of MIF, as a top in cytokines related to inflammation.

• Journal of Pharmacopuncture
• /
• v.10 no.3
• /
• pp.21-28
• /
• 2007

Aim This study was done to investigate whether SPP has inhibitory effects on the activation of RAW 264.7 cells. Method In tumor necrosis factor-a (TNF-a)/ interleukin-1b (IL-1b) and IL-6, the mRNA expression of molecular indicators related to inflammatory changes of the Reumatoid Arthritis (RA) were examined using quantitative real-time PCR. Results The treatment of SPP significantly suppressed the expression of proinflammatory cytokines and chemokines such as TNF-a, IL-1b, IL-6 compared with the control. The expression of NOS-II was considerably reduced, which was accompanied by a reduction in the production of nitric oxide (NO). It also reduced the expression of $TNF-{\alpha}$ in serum of Balb/c mice compared with control group. Conclusion SPP is an effective herbal material for suppressing the inflammation related cytokines of RAW 264.7 cells.

• Animal cells and systems
• /
• v.12 no.4
• /
• pp.193-201
• /
• 2008

The eventual goal of tumor immunotherapy is to develop a vaccine inducing a specific anti-tumor immunity. Cytokine gene therapy is an effective way at least in animal models, but limited efficacy and various side effects obstruct clinical applications. In this study, we developed a tumor vaccine expressing a membrane-bound form of IL-2(mbIL-2) and SDF-1 in B16F10 melanoma cells. The tumor clones expressing mbIL-2 showed reduced tumorigenicity, and additional expression of SDF-1 to mbIL-2 expressing tumor cells caused more severe reduction in tumorigenicity. However, expression of the SDF-1 alone did not affect on the tumorigenicity, probably because of limited production of SDF-1 in the SDF-1 transfected clones. When the mice once rejected mbIL-2/SDF-1 expressing tumor clone were re-challenged with wild type B16F10 tumor cells, all of the mice survived. This result suggests that mbIL-2/SDF-1 tumor clone is effective in inducing systemic anti-tumor immunity against wild type B16 melanoma. Furthermore, culture supernatant of tumor clones expressing SDF-1 induced lymphocyte migration in vitro. These results, all together, suggest that expression of mbIL-2 and SDF-1 in tumor cells enhances anti-tumor immune responses through different roles; the secreted SDF-1 may function as a chemoattractant to recruit immune cells to tumor vaccine injection site, and the mbIL-2 on tumor cells may provide costimulatory signal for CTL activation in physical contacts.

• Journal of Acupuncture Research
• /
• v.19 no.2
• /
• pp.92-104
• /
• 2002

Objective : Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory disease such as rheumatoid arthritis (RA). Autoimmunity to type II collagen (CII) may involve in the pathogenesis of RA. This study was performed to evaluate the effect of BV on type II collagen induced arthritis (CIA) with the naked eye, a immunohistochemical method and the examination of histology. Method : Male mice were immunized by subcutaneously injection of an $200{\mu}g$ emulsion mixed with bovine CII and complete Freund's adjuvant (CFA) twice for two weeks. In the control group, normal saline was injected, and in the experimental group, BV was applied. Result : The incidence of arthritis, the mean arthritis index and the number of the arthritic limbs of the BV group were all significantly lower than those of the control group. Among the pro-inflammatory cytokines, the production of $TNF-{\alpha}$ in the BV group was also suppressed compared with the control group, but $IL-1{\beta}$ was not. The examination on the histopathology of joints of CIA mice showed the effect of Bee Venom Herbal Acupuncture on the arthritis. Conculusion : Treatment with BV resulted in inhibition of development of arthritis and immune responses to CII.

• IMMUNE NETWORK
• /
• v.24 no.1
• /
• pp.10.1-10.17
• /
• 2024

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

• Biomolecules & Therapeutics
• /
• v.20 no.1
• /
• pp.50-56
• /
• 2012

WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, $PGE_2$, and MMP-13 in IL-$1{\beta}$-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of $PGE_2$, NO, IL-$1{\beta}$, and TNF-${\alpha}$ were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and $PGE_2$ was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. I${\kappa}B$B signaling pathways were inhibited by WIN-34B, and the migration of NF-${\kappa}B$ into the nucleus was inhibited, which is consistent with the degradation of $I{\kappa}B-{\alpha}$. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators.

• IMMUNE NETWORK
• /
• v.11 no.5
• /
• pp.288-298
• /
• 2011

Background: Salvia miltiorrhiza (SM) has been used to treat inflammatory diseases including edema and arthritis; however, the anti-inflammatory mechanism of SM action remains unresolved. Methods: The effects of an ethanol extract of SM (ESM) on pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and NO, and on anti-inflammatory cytokines including IL-4, IL-10, TGF-${\beta}$, and IL-1Ra have been studied in an attempt to elucidate the anti-inflammatory mechanism in murine macrophages. Results: ESM inhibited the production of pro-inflammatory cytokines via down-regulation of gene and protein expression whereas it increased the anti-inflammatory cytokines. Furthermore, ESM inhibited the expression of the chemokines, RANTES and CX3CL1, as well as of inflammatory mediators such as TLR-4 and $11{\beta}$-HSD1. Conclusion: These results indicated that the regulatory effects of ESM may be mediated though the suppression of pro-inflammatory cytokines as well as the induction of anti-inflammatory cytokines. Consequently, we speculate that ESM has therapeutic potential for inflammation-associated disorders.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.21 no.4
• /
• pp.69-89
• /
• 2008

Purpose: This study was performed to evaluate anti-oxidant activities and anti-inflammatory effects of Sungyoutanggagambang(SYTG). Methods: In the study of anti-oxidant activities. SYTG was investigated by DPPH radical scavenger activity. superoxide dismutase activity and superoxide anion radical scavenger activity. In the study of anti-inflammatory effects. SYTG was investigated using cultured cells and murine models. As for the parameters of inflammation. levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were measured in mouse lung fibroblast cells(mLFCs) and RAW264.7 cells. Results: Prior to the experiment. we investigated the security of SYTG by measuring GOT and GPT in serum. 1. SYTG showed high antioxidant activity in a concentration-dependent degree by measured scavenging activity of DPPH free radical, superoxide dismutase and superoxide anion radical. 2. SYTG inhibited IL-1$\beta$, IL-6. TNF-$\alpha$, COX-2 and NOS-II mRNA expression as compared with the control group in a concentration-dependent degree in RAW264.7 cell line. 3. SYTG inhibited IL-1$\beta$, IL-6 production significantly at 100 ${\mu}g/ml$ and TNF-$\alpha$ production significantly at 50, 100 ${\mu}g/ml$ as compared with the control group in RA W264.7 cell line. 4. SYTG inhibited IL-1$\beta$, and IL-6 production significantly as compared with the control group in serum of acute inflammation-induced mice. and decreased IL-1$\beta$, IL-6 production in spleen tissue. and also decreased IL-1$\beta$, IL-6 production in liver tissue. Conclusion: These results suggest that SYTG can be useful in treating diverse female diseases caused by inflammation such as endometrosis, myoma, pelvic congestion. chronic cervicitis, chronic pelvic inflammatory disease and so on.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.22 no.3
• /
• pp.83-98
• /
• 2009

Purpose: This study was performed to evaluate the anti-inflammatory effect of Eungapbang extract (EGB). Methods: To evaluate the anti-inflammatory effects of EGB, we nourished RAW 264.7 cell lines in the laboratory dish. Next, inflammatory cytokine concentrations were analyzed. Then, sera were prepared from blood after lipopolysaccharide (LPS) injection in chemically induced mouse models of intestinal inflammation, and Interleukin-1${\beta}$ (IL-1${\beta}$), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-${\alpha}$) were measured using ELISA kits. Results: 1. EGB significantly suppressed the expression levels of IL-1${\beta}$ and NOS-II genes at 100, 50 and 10 ${\mu}g/m{\ell}$ concentrations, and IL-6, TNF-${\alpha}$ and COX-2 mRNAs at 100 and 50 ${\mu}g/m{\ell}$ concentrations. 2. EGB significantly reduced the production level of IL-1${\beta}$ and TNF-${\alpha}$ at 100${\mu}g/m{\ell}$ concentrations, and IL-6 at 100 and 50 ${\mu}g/m{\ell}$ concentrations. 3. EGB significantly decreased the production level of IL-1${\beta}$ and IL-6 in sera of acute inflammation induced mice. 4. EGB could suppress the expression level of IL-1${\beta}$ and IL-6 mRNA in spleen tissues in acute inflammation induced mice. Conclusion: On the basis of the above results, it is confirmed that the anti-inflammatory effects of EGB were recognized. Therefore, EGB is recommended as promising therapy for treatment of such ailments as pelvic inflammatory disease.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.5
• /
• pp.1233-1242
• /
• 2007

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which might be mediated by the altered activation of Immune system, ultimately leading to the destruction of cartilage and bone. To examine effects of GHS on rheumatoid arthritis DBA/1J mice were immunized with bovine type II collagen to induced arthritis and then treated with GHS once a day for 7 weeks. Oral administration of GHS (200 mg/Kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/Kg), a positive control. The severity of arthritis within the knee joints, which was evaluated by histological assessment of cartilage destruction and pannus formation, was also lowered by GHS. The production of TNF-and IL-6 in serum was significantly suppressed. The levels of IFN-g in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. The levels of IgG and IgM RA factor were also decreased in the serum. FACS analysis indicated that B cells (in DLN), CD3+ T cells (in spleen, and paw joint), CD11b+Gr-1+ cells (in paw joint), CD3+CD49b(DX5) (in PBMC) were decreased and there was increased proportion of CD3+, CD4+, CD8+, CD4+CD25+ T cells in DLN. In conclusion, our results demonstrates that GHS significantly suppressed the progression of CIA and this action was characterized by the decreased production of TNF-a, IL-6, and rheumatoid factors, and modulations of immune cell populations.