• IMMUNE NETWORK
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• v.22 no.1
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• pp.7.1-7.20
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• 2022

Recently, there have been impressive advancements in understanding of the immune mechanisms underlying cutaneous inflammatory diseases. To understand these diseases on a deeper level and clarify the therapeutic targets more precisely, numerous studies including in vitro experiments, animal models, and clinical trials have been conducted. This has resulted in a paradigm shift from non-specific suppression of the immune system to selective, targeted immunotherapies. These approaches target the molecular pathways and cytokines responsible for generating inflammatory conditions and reinforcing feedback mechanisms to aggravate inflammation. Among the numerous types of skin inflammation, psoriasis and atopic dermatitis (AD) are common chronic cutaneous inflammatory diseases. Psoriasis is a IL-17-mediated disease driven by IL-23, while AD is predominantly mediated by Th2 immunity. Autoimmune bullous diseases are autoantibody-mediated blistering disorders, including pemphigus and bullous pemphigoid. Alopecia areata is an organ-specific autoimmune disease mediated by CD8⁺ T-cells that targets hair follicles. This review will give an updated, comprehensive summary of the pathophysiology and immune mechanisms of inflammatory skin diseases. Moreover, the therapeutic potential of current and upcoming immunotherapies will be discussed.

• East Asian mathematical journal
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• v.32 no.1
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• pp.139-152
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• 2016

Inflammatory Bowel Disease(IBD) is chronic, relapsing, immune mediated disorder. The exact cause of IBD is still unknown. The immune system is known to play important role in the dynamics of IBD. We focus on relation between T cells and cytokines in immune system that leads to IBD. In this paper, we propose a mathematical model describing IBD under considering immune mediated disorder by using ordinary differential equations. The existence and stability of the model are established, where an applicable basin of attraction are calculated and examined. Some numerical simulations are presented to verify the proposed results and as changing parameter values given by sensitivity analysis, we show how to change dynamic behaviors of the model.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.479-484
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• 2015

NOD2 (nucleotide-binding and oligomerization domain 2) was initially reported as a susceptibility gene for Crohn's disease, with several studies focused on elucidating its molecular mechanism in the progression of Crohn's disease. We now know that NOD2 is an intracellular bacterial sensing receptor, and that MDP-mediated NOD2 activation drives inflammatory signaling. Various mutations in NOD2 have been reported, with NOD2 loss of function being associated with the development of Crohn's disease and other autoimmune diseases. These results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function. Atherosclerosis is a chronic inflammatory disease of the arterial wall; its pathologic progression is highly dependent on the immune balance. This immune balance is regulated by infiltrating monocytes and macrophages, both of which express NOD2. These findings indicate a potential role of NOD2 in atherosclerosis. The purpose of this review is to outline the known roles of NOD2 signaling in the pathogenesis of atherosclerosis.

• Journal of Life Science
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• v.23 no.3
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• pp.448-461
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• 2013

Inflammatory bowel disease, known as Crohn's disease and ulcerative colitis, is an unexplained disease characterized by chronic inflammation that repeats a cycle of relapse, improvement, and complications. The cause of inflammatory bowel disease is not clearly known, but it is predicted that a complex of various factors precipitate its occurrence. In particular, inflammatory mediators, such as cytokine, induce an increase in cell-mediated inflammatory responses. Focal tissue damage then occurs in the intestinal mucosa because of the weakening of the immune-modulating functions of cotton. Immune and inflammatory responses do not decrease appropriately but continue until they lead to chronic inflammation. Current research has focused on the cytokine genes, which have important roles in these inflammatory responses. Cytokine is a glycoprotein that is produced mostly in activated immune cells. It connects the activation, multiplication, and differentiation between immune cells, which causes focal tissue damage and inflammatory response. Moreover, butyrate, which originates in dietary fiber and plays an important role in the structure and function of the intestinal area, shows control functions in the intestinal immune system by decreasing the proinflammatory cytokine and increasing the anti-inflammatory cytokine. Therefore, this research investigated the molecular mechanism of the anti-inflammatory effects of butyrate to comprehend the cytokine controlling abilities of butyrate in the immune cells. Butyrate is expected to have potential in new treatment strategies for inflammatory bowel disease.

• Journal of Veterinary Clinics
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• v.26 no.5
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• pp.433-440
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• 2009

High levels of inflammatory cytokines were proposed contributors to the pathogenesis of a various inflammatory skin disorders. Therefore, investigating the immune response of the inflammatory skin disorder allows a better understanding of pathogenesis of a various inflammatory skin disorders and therapeutic approaches. The aim of this study was to analyze of the immune response in dogs with chronic inflammatory skin disease. To this aim, the present study evaluated relative mRNA expression of canine $IFN-{\gamma}$, IL-4, $TGF-{\beta}$ and IL-10 using TaqMan realtime PCR assays and semi-quantitative RT-PCR in freshly isolated peripheral blood mononuclear cells from twenty dogs with chronic inflammatory skin disease and ten normal dogs. The relative mRNA expression levels of IL-4 mRNA were significantly higher in dogs with chronic inflammatory skin disease than those in normal dogs (P < 0.01). The results of present study also showed a tendency towards increased expression of IL-10 transcripts in dogs with chronic inflammatory skin disease. However, there were no significant differences in the levels $IFN-{\gamma},\;TGF-{\beta}$ between normal and chronically inflammed dogs. In addition, the concentration of serum IgE was significantly increased in dogs with chronic inflammatory skin disease compared with those in normal dogs (P < 0.01). In histopathological examination, we found that there were markedly increased mast cell counts in chronically inflammed dogs (P < 0.05). These results suggest that the pathogenesis of chronic inflammatory skin disease might be associated with a T-cell mediated inflammatory responses characterized by a Th2-skewed immune response. Based on these results, the modulation of Th1/Th2 balance may be an effective therapeutic strategy for the treatment of chronic inflammatory skin disease.

• Clinical and Experimental Pediatrics
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• v.63 no.9
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• pp.337-344
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• 2020

Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is reportedly lower in Asia than in Western countries, the rapid increase in the incidence of IBD has drawn attention to its etiology, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may interact with the immune system, and the imbalance of this relationship may lead to immune dysregulation in IBD. Changes in diet or alterations in the composition of the intestinal microbiota may be associated with the increasing incidence of IBD in Asia. Here, we aim to review recent studies on the role of diet and intestinal microbiota in IBD pathogenesis and the results of the investigations performed to modulate these factors.

• Tuberculosis and Respiratory Diseases
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• v.79 no.1
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• pp.5-13
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• 2016

Chronic obstructive pulmonary disease (COPD) is a chronic and progressive inflammatory disease of the airways and lungs that results in limitations of continuous airflow and is caused by exposure to noxious gasses and particles. A major cause of morbidity and mortality in adults, COPD is a complex disease pathologically mediated by many inflammatory pathways. Macrophages, neutrophils, dendritic cells, and CD8+ T-lymphocytes are the key inflammatory cells involved in COPD. Recently, the non-coding small RNA, micro-RNA, have also been intensively investigated and evidence suggest that it plays a role in the pathogenesis of COPD. Here, we discuss the accumulated evidence that has since revealed the role of each inflammatory cell and their involvement in the immunopathogenesis of COPD. Mechanisms of steroid resistance in COPD will also be briefly discussed.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.283-288
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• 2013

The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.

• Natural Product Sciences
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• v.17 no.3
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• pp.239-244
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• 2011

Immediate-type hypersensitivity is involved in many allergic diseases such as asthma, allergic rhinitis and anaphylaxis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. Stimulation of mast cells releases inflammatory mediators, such as histamine and pro-inflammatory cytokines with immune regulatory properties. We investigated the effect of the aqueous extract of Schizonepeta tenuifolia (AEST) (Labiatae) on the immediate-type allergic reaction. AEST inhibited compound 48/80-induced systemic allergic reaction. AEST attenuated immunoglobulin E (IgE)-mediated skin allergic reaction and histamine release from human mast cell line (HMC-1) cells. In addition, AEST decreased the gene expression and secretion of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated HMC-1 cells. Our results indicate that AEST inhibits the mast cell-derived allergic reactions and involvement of histamine and pro-inflammatory cytokines in these effects.

• IMMUNE NETWORK
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• v.21 no.1
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• pp.10.1-10.13
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• 2021

The coronavirus disease 2019 (COVID-19) pandemic (severe acute respiratory syndrome coronavirus 2) is a global infectious disease with rapid spread. Some patients have severe symptoms and clinical signs caused by an excessive inflammatory response, which increases the risk of mortality. In this study, we reanalyzed scRNA-seq data of cells from bronchoalveolar lavage fluids of patients with COVID-19 with mild and severe symptoms, focusing on Ab-producing cells. In patients with severe disease, B cells seemed to be more activated and expressed more immunoglobulin genes compared with cells from patients with mild disease, and macrophages expressed higher levels of the TNF superfamily member B-cell activating factor but not of APRIL (a proliferation-inducing ligand). In addition, macrophages from patients with severe disease had increased pro-inflammatory features and pathways associated with Fc receptor-mediated signaling, compared with patients with mild disease. CCR2-positive plasma cells accumulated in patients with severe disease, probably because of increased CCL2 expression on macrophages from patients with severe disease. Together, these results support the hypothesis that different characteristics of B cells might be associated with the severity of COVID-19 infection.