• Clinical and Experimental Pediatrics
• /
• v.63 no.7
• /
• pp.239-250
• /
• 2020

The novel coronavirus disease 2019 (COVID-19) is spreading globally. Although its etiologic agent is discovered as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), there are many unsolved issues in COVID-19 and other infectious diseases. The causes of different clinical phenotypes and incubation periods among individuals, species specificity, and cytokine storm with lymphopenia as well as the mechanism of damage to organ cells are unknown. It has been suggested that in viral pneumonia, virus itself is not a direct cause of acute lung injury; rather, aberrant immune reactions of the host to the insults from viral infection are responsible. According to its epidemiological and clinical characteristics, SARS-CoV-2 may be a virus with low virulence in nature that has adapted to the human species. Current immunological concepts have limited ability to explain such unsolved issues, and a presumed immunopathogenesis of COVID-19 is presented under the protein-homeostasis-system hypothesis. Every disease, including COVID-19, has etiological substances controlled by the host immune system according to size and biochemical properties. Patients with severe pneumonia caused by SARS-CoV-2 show more severe hypercytokinemia with corresponding lymphocytopenia than patients with mild pneumonia; thus, early immunomodulator treatment, including corticosteroids, has been considered. However, current guidelines recommend their use only for patients with advanced pneumonia or acute respiratory distress syndrome. Since the immunopathogenesis of pneumonia may be the same for all patients regardless of age or severity and the critical immune-mediated lung injury may begin in the early stage of the disease, early immunomodulator treatment, including corticosteroids and intravenous immunoglobulin, can help reduce morbidity and possibly mortality rates of older patients with underlying conditions.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.4
• /
• pp.866-874
• /
• 2006

Atopic dermitiis(AD) is a chronic inflammatory skin disease, which requires safe and effective medicinal therapy. Over production of Th2 cytokines and chemokines as well as IgE, which are mediated by highly activated immune cells, have been considered as pathologic factors in this disease. We found that Gamipaidok-san(GPDS), which is a traditional herbal medicine clinically prescribing for atopic dermitis patients in the hospital, has suppressive effects on the development of DNC8 induced dermatitis in Nc/Nga atopic model. Oral administration of GPDS at the concentration of 250 mg/Kg for 12 weeks significantly suppressed the clinical severity of the dermatitis including pruities, edema, eczematous and dryness. Histological examination revealed that thickness of dermis and epidermis were considerably reduced, and the number of infiltrated inflammatory immune cells including mast cells, CCR3+, and CD4+ T cells were decreased in the affected skin and ear, and consistantly, the number of CD3+/CCR3+ cells in Iymph nodes were decreased. The levels of Th2 cytokines produced by activated splenocyte from atopic mice were also down-regulated by GPDS. Furthermore, the serum levels of IgE were considerably reduced, which accompanied by a decrease in the number of B220+IgE+ B cells in the Iymph nodes. Taken together, these results suggested that oral administration of GPDS, a traditional herbal medicine, has suppressive effects on atopic dermitis of Nc/Nga mouse by the modulation of the immune system, therefore GPDS has potential as a natural therapeutic for treatment of atopic dermatitis.

• Korean Journal of Poultry Science
• /
• v.38 no.2
• /
• pp.155-164
• /
• 2011

The use of antimicrobials will be soon removed due to an increase of occurrence of antibiotic-resistant bacteria or ionophore-resistant Eimeria species in poultry farms and consumers' preference on drug-free chicken meats or eggs. Although dietary antimicrobials contributed to the growth and health of the chickens, we do not fully understand their interrelationship among antimicrobials, gut microbiota, and host immunity in poultry. In this review, we explored the current understanding on the effects of antimicrobials on gut microbiota and immune systems of chickens. Based on the published literatures, it is clear that antibiotics and antibiotic ionophores, when used singly or in combination could influence gut microbiota. However, antimicrobial effect on gut microbiota varied depending on the samples (e.g., gut locations, digesta vs. mucosa) used and among the experiments. It was noted that the digesta vs. the mucosa is the preferred sample with the results of no change, increase, or decrease in gut microbiota community. In future, the mucosa-associated bacteria should be targeted as they are known to closely interact with the host immune system and pathogen control. Although limited, dietary antimicrobials are known to modulate humoral and cell-mediated immunities. Ironically, the evidence is increasing that dietary antimicrobials may play an important role in triggering enteric disease such as gangrenous dermatitis, a devastating disease in poultry industry. Future work should be done to unravel our understanding on the complex interaction of host-pathogen-microbiota-antimicrobials in poultry.

• IMMUNE NETWORK
• /
• v.19 no.1
• /
• pp.1.1-1.13
• /
• 2019

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of antimicrobial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72^-/- mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.

• IMMUNE NETWORK
• /
• v.2 no.4
• /
• pp.189-194
• /
• 2002

Although the exact mechanism responsible for the pathogenesis of psoriasis is unclear, interferon-${\gamma}$ producing type 1 T cells have been reported to play a significant role. Infiltrating activated type 1 T cells in the lesions are believed to be responsible for stimulating keratinocytes, which produce many cytokines and growth factors. The hyperproliferative epidermis is understood to be the result of either the cytokines produced by the intraepidermal T cells or the reactive phenomenon after keratinocyte damage. The microenvironment in psoriatic lesions deviates toward the type 1 status, because of the increased type 1 cytokines and either the decreased or unchanged type 2 cytokines observed in psoriatic lesions. Therefore, this review focused on a T-cell-mediated immunological basis for the current hypothesis of the psoriasis pathogenesis.

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

• Genomics & Informatics
• /
• v.2 no.3
• /
• pp.126-130
• /
• 2004

T helper-type 2 cytokines, such as IL-4 and IL-13, may play a central role in allergic diseases. The protein known as signal transducers and activators of transcription 6 (STAT6) is a key transcription factor involved in both IL-4- and -13-mediated biological responses. Two polymorphisms of the STAT 6 gene (exon 1 and G2964A variant) have been found. We investigated whether these STAT6 gene polymorph isms were associated with allergic rhinitis. Blood samples for genetic analysis were obtained from 285 individuals with allergic rhinitis and from 271 healthy subjects without atopic disease. The G2964A variant of the STAT6 gene was genotyped using PCR-RFLP analysis. The GT repeat polymorphism in exon 1 of the STAT6 gene was genotyped by fragment analysis. There was no association between the 2964A variant and GT repeat polymorphism in exon 1 of the STAT6 and allergic rhinitis in a Korean population (both p > 0.05). Our results suggest that a combination of STAT6 gene polymorphisms is not a useful marker for predicting allergic rhinitis.

• IMMUNE NETWORK
• /
• v.19 no.1
• /
• pp.5.1-5.12
• /
• 2019

Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.34 no.1
• /
• pp.28-35
• /
• 2008

Purpose: The nitric oxide (NO) release by inducible nitric oxide synthase (iNOS) is the key events in macrophage response to lipopolysaccharide (LPS) which is suggested to be a crucial mediator for inflammatory and innate immune responses. NO is an important mediator involved in many host defense action and may also lead to a harmful host response to bacterial infection. However, given the importance of iNOS in a variety of pathophysiological conditions, control of its expression and signaling events in response to LPS has been the subject of considerable investigation. Materials and Methods: The Raw264.7 macrophage cell line was used to observe LPS-stimulated iNOS expression. The expression of iNOS is observed by Western blot analysis and real-time RT-PCR. Protein kinase C $(PKC)-{\alpha}$ overexpressing Raw264.7 cells are established to determine the involvement of $PKC-{\alpha}$ in LPS-mediated iNOS expression. $NF-{\kappa}B$ activity is measured by $I{\kappa}B{\alpha}$ degradation and $NF-{\kappa}B$ luciferase activity assay. Results: We found that various PKC isozymes regulate LPS-induced iNOS expression at the transcriptional and translational levels. The involvement of $PKC-{\alpha}$ in LPS-mediated iNOS induction was further confirmed by increased iNOS expression in $PKC-{\alpha}$ overexpressing cells. $NF-{\kappa}B$ dependent transactivation by LPS was observed and $PKC-{\alpha}$ specific inhibitory peptide abolished this activation, indicating that $NF-{\kappa}B$ activation is dependent on $PKC-{\alpha}$. Conclusion: Our data suggests that $PKC-{\alpha}$ is involved in LPS-mediated iNOS expression and that its downstream target is $NF-{\kappa}B$. Although $PKC-{\alpha}$ is a crucial mediator in the iNOS regulation, other PKC isozymes may contribute LPS-stimulated iNOS expression. This finding is needed to be elucidated in further study.

• Journal of Chest Surgery
• /
• v.50 no.2
• /
• pp.114-118
• /
• 2017

Kimura disease (KD) is an immune-mediated chronic inflammatory disease of unknown etiology. KD has many complications associated with hypereosinophilia, including various forms of allergic reactions and eosinophilic lung disease. Additionally, hypereosinophilia is associated with hypercoagulability, which may lead to thromboembolic events. A 36-year-old man with KD presented with acute limb ischemia and coronary artery occlusion. He underwent thrombectomy, partial endarterectomy of both popliteal arteries, and coronary artery stent insertion. KD is a systemic disease that affects many organs and presents with thromboembolism and vasculitis. In a patient with KD, physicians should evaluate the vascular system, including the coronary arteries.