• Korean Journal of Biological Psychiatry
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• v.18 no.4
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• pp.169-175
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• 2011

Stress, a risk factor of major depression induces cytokine mediated inflammation and decreased neurogenesis. In patients with major depression, significant increases of pro-inflammatory cytokines have been consistently reported. The pro-inflammatory cytokines can stimulate the hypothalamic-pituitary-adrenal (HPA) axis to release glucocorticoids. In the brain, microglia and play a role of immune activation in response to stress. Increased pro-inflammatory cytokine play a role in restricting neurogenesis in the brain. Although neurogenesis may not be essential for the development of depression, it may be required for clinically effective antidepressant treatment. Hence, stimulation of neurogenesis is regarded as a promising strategy for new antidepressant targets. This review introduces changes in neurotransmitter, cytokine and neurogenesis in major depression and explores the possible relationship between pro-inflammatory cytokines and neurogenesis related to stress in major depression.

• BMB Reports
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• v.48 no.3
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• Korean Journal of Biological Psychiatry
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• v.15 no.3
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• pp.175-185
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• 2008

Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

• Parasites, Hosts and Diseases
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• v.49 no.3
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• pp.285-290
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• 2011

Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A $^{51}Cr$ release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-${\alpha}$, IL-6, and IL-$1{\beta}$, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.2
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• pp.101-108
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• 2006

The aim of the present study was to elucidate whether gallic acid could modulate the inflammatory allergic reaction and to study its mechanism of action Gallic acid inhibited compound 48/80- or immunoglobulin E (IgE)-induced histamine release from mast cells. The inhibitory effect of gallic acid on the histamine release was mediated by modulation of cAMP and intracellular calcium. Gallic acid decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated pro-inflammatory cytokine gene expression and production such as TNF- ${\alpha}$ and IL-6 in human mast cells, and the inhibitory effect of gallic acid was on dependent nuclear factor- ${\kappa}$B and p38 mitogen-activated protein kinase. Our findings provide evidence that gallic acid inhibits mast cell-derived inflammatory allergic reaction by blocking histamine release and pro-inflammatory cytokine expression.

• East Asian mathematical journal
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• v.38 no.3
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• pp.357-363
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• 2022

Immunological imbalance eventually results in the development of various diseases. A typical example is an imbalance of cytokines with immunomodulatory abilities. In this paper, we propose a two-variable delay model to anti-pro-inflammatory cytokine therapy for autoimmune diseases, which are caused by an imbalance between the pro and anti-inflammatory cytokines. The interaction between pro- and anti-inflammatory cytokines were modeled mathematically to investigate the relevance of cytokines in disease processes. The delay time was estimated to maintain the stability of a biologically important steady state. In particular, the effects of delay with anti-pro-inflammatory cytokines therapy in autoinflammatory diseases were studied.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.413-420
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• 2015

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing ${\alpha}2$ adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce $Ca^{2+}$ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger $Ca^{2+}$ peak or increase in the presence or absence of external $Ca^{2+}$. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced $[Ca^{2+}]_i$ signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.124-129
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• 2005

Pro-inflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin-12 (IL-12) and interleukin $(IL-1)-{\beta}$, play a key role in causing inflammatory diseases, which are rheumatoid arthritis, Crohn's disease and sepsis. Accumulating evidences suggest that low level laser irradiation (LLLI) may have an anti-inflammatory action. However, there are few data regarding down regulation of Th1 immune response by using the diod typed laser emitting device for human patients. As a fundamental step in order to address this issue, we investigated immunological impact of the low level laser irradiation (10 mw laser diode with a wavelength of 630 nm) on expression of pro-inflammatory cytokines in murine immunocytes (splenocytes and peritoneal macrophages) in vitro. The LLLI on lipopolysaccharide (LPS 100 ng/ml)-stimulated murine splenocytes and macrophages, clearly down regulated mRNA expression of $TNF-{\alpha}$ and IL-12 in dose-dependent manner. In addition, LLLI significantly inhibits the NO production in the LPS-stimulated murine macrophages. This data suggests that LLLI (wavelength of 630 nm) may exert an anti-inflammatory action via modulation of pro-inflammatory cytokine and NO production pathway.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.202-210
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• 2018

Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum flower (ADF) extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor NF-${\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADF significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-${\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the flower extract has potential therapeutic benefits against various inflammatory diseases.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.3
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• pp.176-182
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• 2016

When inflammatory reaction is in progress, the macrophages release inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and product inflammatory mediators, including inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2). We conducted this study to evaluate the anti-inflammatory efficacy on each water extract of Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex, and to investigate whether they inhibit the expression of pro-inflammatory cytokine. Acanthopanacis cortex, Achyranthes radix, and Eucommiae cortex were extracted with water and freeze-dried. Acanthoside D, 20-hydroxyecdysone, and pinoresinol diglucoside as an index material were analyzed by high-performance liquid chromatography (HPLC) to ensure that the components of each extracts were extracted well. RAW 264.7 cell line, stimulated with lipopolysaccharide (LPS) to cause an inflammatory response, was treated with each water extract at various concentrations to determine the anti-inflammatory efficacy. Then, the anti-inflammatory efficacy was confirmed by a nitric oxide (NO) assay, and the mRNA expression levels of pro-inflammatory cytokines were measured by real time PCR. As a result, the indicator materials were detected from each extract, and Acanthopanacis cortex water extract (ACWE) and Achyranthes radix water extract (ARWE) were shown to have a high activity than Eucommiae cortex water extract (ECWE) in NO assay. In Korea, traditionally it prescribed a combination of medicinal herbs. This study confirmed the anti-inflammatory response of these medicinal plants in arthritis and its synergistic effect when used in combination with western medicine.