• The Journal of Korean Medicine
• /
• v.17 no.2 s.32
• /
• pp.227-236
• /
• 1996

The effect of Ligustrum Lucidum(LL) on the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages were investigated. Stimulation of the cells with LL in the presence or absence of interferon-r(IFN-r) resulted in the increased accumulation of nitrite in the medium. To further examine the mechanism of LL induced. NO Synthesis, we evaluated the secretion of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ by LL in murine macrophages. Treatment of LL increased the secretion of bioactive $TNF-{\alpha}$ in cultured medium. In addition, LL induced NO production was decreased by the treatment of anti-murine $TNF-{\alpha}$. neutralizing antibodies, indicating that LL induced superoxide production was decreased by the treatment of anti-murine $TNF-{\alpha}$ neutralizing antibodies. These data suggested that LL induced superoxide production was related to $TNF-{\alpha}$ secretion. In conclusion, our results indicates that LL may enhance innate immune response and be applied as a immunoregulating drug improving phagocytosis.

• Journal of Veterinary Clinics
• /
• v.25 no.6
• /
• pp.440-446
• /
• 2008

Glucocorticoids (GCs) are the most widely used immunosuppressive agents, but animals treated with GCs may experience deleterious side effects which limit their use in many clinical conditions. In the present study, we examined whether methylprednisolone sodium succinate (MPSS), a glucocorticoid, modulates circulating leukocyte numbers, phagocytic capacity and oxidative burst activity (OBA) of canine peripheral blood phagocytes, and whether tumor necrosis factor-alpha (TNF-$\alpha$) release is affected by MPSS injection. Neutrophilia and monocytosis were induced by the administration of a high dose of MPSS, which is the recommended protocol for canine patients with acute spinal cord injury. The injection of MPSS decreased the phagocytic capacity of canine PMNs but not PBMCs, and recovered 12 hours (hr) after the completion of MPSS dosing. The OBA of both PMNs and PBMCs was suppressed by MPSS, and restored 24 hr after the completion of dosing. The lipopolysaccharide-induced TNF-α release by PBMCs but not PMNs exposed to MPSS was reduced 12 hr after the completion of dosing, and recovered 48 hr after the completion of dosing. These results suggest that the application of MPSS protocol inhibits the innate immune functions of canine peripheral blood phagocytes for short time relatively.

• Parasites, Hosts and Diseases
• /
• v.54 no.5
• /
• pp.679-684
• /
• 2016

Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-${\kappa}B$-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.

• IMMUNE NETWORK
• /
• v.22 no.4
• /
• pp.32.1-32.20
• /
• 2022

Sjögren syndrome (SS) is a chronic autoimmune disorder that primarily targets the salivary and lacrimal glands. The pathology of these exocrine glands is characterized by periductal focal lymphocytic infiltrates, and both T cell-mediated tissue injury and autoantibodies that interfere with the secretion process underlie glandular hypofunction. In addition to these adaptive mechanisms, multiple innate immune pathways are dysregulated, particularly in the salivary gland epithelium. Our understanding of the pathogenetic mechanisms of SS has substantially improved during the past decade. In contrast to viral infection, bacterial infection has never been considered in the pathogenesis of SS. In this review, oral dysbiosis associated with SS and evidence for bacterial infection of the salivary glands in SS were reviewed. In addition, the potential contributions of bacterial infection to innate activation of ductal epithelial cells, plasmacytoid dendritic cells, and B cells and to the breach of tolerance via bystander activation of autoreactive T cells and molecular mimicry were discussed. The added roles of bacteria may extend our understanding of the pathogenetic mechanisms and therapeutic approaches for this autoimmune exocrinopathy.

• Development and Reproduction
• /
• v.17 no.4
• /
• pp.311-319
• /
• 2013

Fish larvae are immediately exposed to microbes from hatching to maturation of their lymphoid organs, therefore effective innate mechanisms is very important for survival in such an environment. The key component of innate immune system, C3 is central protein of all activation pathways of the complement system, leading to inflammatory reactions, such as opsonisation, chemotaxis, and cell lysis of pathogens. Although, innate mechanisms is essential for survival in the early stage of development, little is known about defence mechanisms. In this study, the alignment analysis showed that amino acid sequence of C3 from olive flounder liver EST homologous to other known C3 sequences with 73-99% identity. Also, we examined the tissue distribution of olive flounder C3 and analyzed expression pattern from the fertilized egg until 28 days post hatching. As a result, olive flounder C3 mRNA was expressed only in the liver and the mRNA level more increased as developmental proceed during the early stage. These results may suggest that olive flounder C3 plays an important function in the early immune response of olive flounder larvae.

• Parasites, Hosts and Diseases
• /
• v.54 no.6
• /
• pp.711-717
• /
• 2016

Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of $pro-IL-1{\beta}$. To elucidate the role of inflammasome components in T. gondiiinfected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine $IL-1{\beta}$ secretion. The results revealed a significant upregulation of $IL-1{\beta}$ after T. gondii infection. T. gondii infection also upregulated the expression of inflammasome sensors, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and NAIP, in a time-dependent manner. The infection also upregulated inflammasome adaptor protein ASC and caspase-1 mRNA levels. From this study, we newly found that T. gondii infection regulates NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and neuronal apoptosis inhibitor protein (NAIP) gene expressions in THP-1 macrophages and that the role of the inflammasome-related genes may be critical for mediating the innate immune responses to T. gondii infection.

• Parasites, Hosts and Diseases
• /
• v.57 no.3
• /
• pp.225-232
• /
• 2019

Innate lymphoid cells (ILCs) are key players during an immune response at the mucosal surfaces, such as lung, skin, and gastrointestinal tract. Giardia lamblia is an extracellular protozoan pathogen that inhabits the human small intestine. In this study, ILCs prepared from the lamina propria of mouse small intestine were incubated with G. lamblia trophozoites. Transcriptional changes in G. lamblia-exposed ILCs resulted in identification of activation of several immune pathways. Secretion of interleukin (IL)-17A, IL-17F, $IL-1{\beta}$, and interferon-${\gamma}$ was increased, whereas levels of IL-13, IL-5, and IL-22, was maintained or reduced upon exposure to G. lamblia. Goup 3 ILC (ILC3) was found to be dominant amongst the ILCs, and increased significantly upon co-cultivation with G. lamblia trophozoites. Oral inoculation of G. lamblia trophozoites into mice resulted in their presence in the small intestine, of which, the highest number of parasites was detected at the 5 days-post infection. Increased ILC3 was observed amongst the ILC population at the 5 days-post infection. These findings indicate that ILC3 from the lamina propria secretes IL-17 in response to G. lamblia, leading to the intestinal pathology observed in giardiasis.

• Clinical and Experimental Reproductive Medicine
• /
• v.45 no.4
• /
• pp.154-162
• /
• 2018

Objective: The fallopian tubes play a critical role in the early events of fertilization. The rapid innate immune defense is an important part of the fallopian tubes. Toll-like receptor 3 (TLR3), as a part of the innate immune system, plays an important role in detecting viral infections. In this basic and experimental study, the effect of sex hormones on the function of TLR3 in the OE-E6/E7 cell line was investigated. Methods: The functionality of TLR3 in this cell line was evaluated by cytokine measurements (interleukin [IL]-6 and IL-1b) and the effects of sex hormones on TLR3 were tested by an enzyme-linked immunosorbent assay kit. Additionally, TLR3 small interfering RNA (siRNA) and a TLR3 function-blocking antibody were used to confirm our findings. Results: The production of IL-6 significantly increased in the presence of polyinosinic-polycytidylic acid (poly(I:C)) as the TLR3 ligand. Using a TLR3-siRNA-ransfected OE-E6/E7 cell line and function-blocking antibody confirmed that cytokine production was due to TLR3. In addition, 17-${\beta}$ estradiol and progesterone suppressed the production of IL-6 in the presence and absence of poly(I:C). Conclusion: These results imply that sex hormones exerted a suppressive effect on the function of TLR3 in the fallopian tube cell line when different concentrations of sex hormones were present. The current results also suggest that estrogen receptor beta and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3, as these two receptors are the main estrogen and progesterone receptors in OEE6/E7 cell line.

• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.55 no.3
• /
• pp.379-385
• /
• 2022

This study was conducted to evaluate the dietary supplementation of citrus byproduct (CBP) on the growth performance, feed utilization, and innate immune responses of juvenile olive flounder Paralichthys olivaceus under low water temperatures (11-15℃). Dietary L-ascorbyl-2-polyphosphate was replaced with graded CBP levels at 0 (Con), 25 (CBP25), 50 (CBP50), 75 (CBP75), and 100% (CBP100). Triplicate groups of juvenile olive flounder were handfed with one of the diets twice a day for 42 days. The growth performance and feed utilization of fish fed with diet containing levels of CBP75 or CBP100 increased significantly compared to those of fish with fed Con. Dietary CBP supplementation increased the protein efficiency ratio in fish. There was no significant differences in innate immune responses between groups, even though CBP supplementation tended to increase. These findings indicate that CBP could be used as a vitamin C source and improve the growth performance of juvenile olive flounder under low water temperatures.

• Molecules and Cells
• /
• v.45 no.10
• /
• pp.702-717
• /
• 2022

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulates beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediates protein interplay between NS5A and IKKε, thereby contributing to NS5A mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.