Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation

Min Jin-Young,Kim Jin Youp,성충만,Kim Seon Tae,조현진,문수진,Cho Sung-Woo,Hong Sang Duk,Ryu Gwanghui,Cho Kyoung Rai,Kim Young Hyo,Park Soo-Kyoung,Kim Dong-Kyu,Lee Dong Hoon,Heo Sung Jae,Lee Ki-Il,Kim Su Jin,Le 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.4

Purpose: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. Methods: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1β, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-β1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. Results: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. Conclusions: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

세신약침(細辛藥鍼)의 천식억제 및 면역조절효과에 대한 실험적 연구

김일구 ( Il Gu Kim ),김영일 ( Young Il Kim ),홍권의 ( Kwon Eui Hong ),임윤경 ( Yun Kyoung Yim ),이현,이병렬 ( Byung Ryul Lee ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.1

Objectives and methods: The aim of this study was to investigate the effect of AHCR(ASARI HERBA CUM RADICE) herbal acupuncture at St36 on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). Two experimental groups were treated with different concentrations(1%, 0.1%) of AHCR-HAS at Chok-samni (St36) for the later 8 weeks (3times/week). Results: 1. Lung weight of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with that of control group. 4. The number of Gr-1+ /CD11b+, CCR3+, CD4+, CD3e+/CD69+, IgE+/B220+ cells in the lungs of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 5. The number of CD8+ cells in the lungs of the mice group treated with AHCR-HA didn`t show significant difference compared with that of control group. 6. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with AHCR-HA decreased significantly compared with that of control group. Conclusion: We conclude that AHCR-HA is effective on OVA-induced asthma in C57BL/6 mouse.

The Leaves of Broussonetia kazinoki Siebold Inhibit Atopic Dermatitis-Like Response on Mite Allergen-Treated Nc/Nga Mice

( Ho Young Lee ),( Hye Kyung Ha ),( Jun Kyoung Lee ),( Sang Joon Park ),( Seung Il Jeong ),( Hyeun Kyoo Shin ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.5

Broussonetia kazinoki Siebold. (B. kazinoki) has long been used in the manufacture of paper in Asian countries. Although B. kazinoki leaves (BK) have been employed in dermatological therapy, use of BK has not been tested in patients with atopic dermatitis (AD). Using Nc/Nga mice, which are genetically predisposed to develop AD-like skin lesions, we confirmed the efficacy of BK in AD treatment. BK extract was applied topically to Dermatophagoides farinae-induced AD-like lesions in Nc/Nga mice, and the effects were assessed both clinically and by measuring skin thickness on the back and ears. We measured the effects of BK extract on plasma levels of IgE and IL-4. We also measured the ability of BK extract to inhibit the secretion of hTARC in HaCaT cells after stimulation by TNF-α and IFN-γ. We found that BK extract significantly reduced ear and dorsal skin thickness and the clinical signs of AD, as well as significantly down-regulating the plasma levels of IgE and IL-4 (p<0.01 for each comparison). Moreover, 500 μg/ mL of BK extract inhibited hTARC secretion in HaCaT cells by activated TNF-α/IFN-γ by about 87%. These findings suggest that topical application of BK extract has excellent potential in the treatment of AD.

Ampelopsis japonica Makino Extract Inhibits the Inflammatory Reaction Induced by Pathogen-Associated Molecular Patterns in Epidermal Keratinocytes

( Mi Ra Choi ),( Dae Kyoung Choi ),( Ki Duck Kim ),( Sue Jeong Kim ),( Dong Il Kim ),( Myung Im ),( Young Lee ),( Young Joon Seo ),( Chang Deok Kim ),( Jeung Hoon Lee ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.3

Background: Keratinocytes are the major cells in epidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been known that pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. Objective: The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs-induced inflammatory reaction of keratinocytes. Methods: The effects of AE were determined using poly (I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. Results: In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated nuclear factor-κB signaling pathway. In imiquimod- induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. Conclusion: These results suggest that AE may be a potential candidate for the treatment of skin inflam-mation. (Ann Dermatol 28(3) 352∼359, 2016)

The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis

Cheon, Yun-Hong,Lee, Seung-Geun,Kim, Mingyo,Kim, Hyun-Ok,Sun Suh, Young,Park, Ki-Soo,Kim, Rock Bum,Yang, Hyun-Su,Kim, Ji-Min,Son, Chang-Nam,Kyoung Park, Eun,Kim, Sang-Hyon,Lee, Sang-Il Elsevier 2018 Brain, behavior, and immunity Vol.73 No.-

<P><B>Abstract</B></P> <P>Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22–4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01–2.53]) and severity of fatigue (OR 1.26 95% CI 1.15–1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one’s capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prevalence of depression in patients with rheumatoid arthritis (RA) was analyzed. </LI> <LI> Risk factors for depression and deterioration of depressive symptoms and were analyzed. </LI> <LI> Depression was related with disease activity in RA. </LI> <LI> Depression in RA was associated with impaired ability to perform activities of daily life. </LI> <LI> Among neurotrophic factors, the level of BDNF was related with depression in RA patients. </LI> <LI> The level of pro-inflammatory cytokines were not related with depression in RA patients. </LI> </UL> </P>

Ampelopsis japonica Makino extract (AE) inhibits the inflammatory reaction induced by pathogen-associated molecular patterns (PAMPs) in epidermal keratinocytes

( Mi Ra Choi ),( Jin Hyup Lee ),( Dae Kyoung Choi ),( Dong Il Kim ),( Hae Eul Lee ),( Myung Im ),( Young Lee ),( Chang Deok Kim ),( Young Joon Seo ),( Jeung Hoon Lee ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Keratinocytes are the major cells inepidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been knownthat pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. Objectives: The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs-induced inflammatory reaction of keratinocytes. Methods: The effects of AE were determined using poly(I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. Results: In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as IL-1モ, IL-6, IL-8 and TNF-メ. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated NF-リB signaling pathway. In imiquimod-induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. Conclusion: These results suggest that AE may be a potential candidate for the treatment of skin inflammation.

세신약침(細辛藥鍼)의 천식억제 및 면역조절효과에 대한 실험적 연구

김일구,김영일,홍권의,이현,이병렬,임윤경,Kim, Il-Gu,Kim, Young-Il,Hong, Kwon-Eui,Lee, Hyeon,Lee, Byung-Ryul,Yim, Yun-Kyoung 경락경혈학회 2004 대한침구의학회지 Vol.21 No.1

Objectives and methods : The aim of this study was to investigate the effect of AHCR(ASARI HERBA CUM RADICE) herbal acupuncture at St36 on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). Two experimental groups were treated with different concentrations(1%, 0.1%) of AHCR-HAS at Chok-samni (St36) for the later 8 weeks (3times/week). Results 1. Lung weight of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with that of control group. 4. The number of $Gr-1^+/CD11b^+,\;CCR3^+,\;CD4^+,\;CD3e^+/CD69^+,\;IgE^+/B220^+$ cells in the lungs of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 5. The number of $CD8^+$ cells in the lungs of the mice group treated with AHCR-HA didn't show significant difference compared with that of control group. 6. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with AHCR-HA decreased significantly compared with that of control group. Conclusion We conclude that AHCR-HA is effective on OVA-induced asthma in C57BL/6 mouse.

Comparison of Cytokine and Nitric Oxide Induction in Murine Macrophages between Whole Cell and Enzymatically Digested Bifidobacterium sp. Obtained from Monogastric Animals

Kim, Dong-Woon,Cho, Sung-Back,Lee, Hyun-Jeong,Chung, Wan-Tae,Kim, Kyoung-Hoon,HwangBo, Jong,Nam, In-Sik,Cho, Yong-Il,Yang, Mhan-Pyo,Chung, Il-Byung The Microbiological Society of Korea 2007 The journal of microbiology Vol.45 No.4

The principal objective of this study was to compare the effects of whole and hydrolyzed cells (bifidobacteria) treated with gastrointestinal digestive enzymes on the activation of cloned macrophages. Seven different strains of Bifidobacterium obtained from swine, chickens, and rats, were digested with pepsin followed by pancreatin and the precipitate (insoluble fraction) and supernatant (soluble fraction) obtained via centrifugation. The RAW 264.7 murine macrophages were incubated with either whole cells, the precipitate, or supernatant at various concentrations. Pronounced increases in the levels of nitric oxide (NO), interleukin $(IL)-1{\beta}$, IL-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$ were observed in the whole cells and precipitates, but these effects were less profound in the supernatants. The precipitates also evidenced a slight, but significant, inductive activity for NO and all tested cytokines, with the exception of $(TNF)-{\alpha}$ in the macrophage model as compared with the whole cells. By way of contrast, $(TNF)-{\alpha}$ production when cultured with whole cells (100 ng/ml) resulted in marked increases as compared with what was observed with the precipitates. The results of this study indicated, for the first time, that digested Bifidobacterium sp. can induce the production of NO and several cytokines in RAW 264.7 murine macrophage cells. In the current study, it was demonstrated that Bifidobacterium strains treated with digestive enzymes, as compared with whole cells, are capable of stimulating the induction of macrophage mediators, which reflects that they may be able to modulate the gastrointestinal immune functions of the host.

상엽약침(桑葉藥鍼)의 천식억제효과(喘息抑制效果)에 대한 실험적 연구

신성찬 ( Sung Chan Shin ),김영일 ( Young Il Kim ),홍권의 ( Kwon Eui Hong ),임윤경 ( Yun Kyoung Yim ),이현 ( Hyun Lee ),이병렬 ( Byung Ryul Lee ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.3

Objective: The aim of this study was to investigate the effect of Mori Folium herbal acupuncture at St36 on ovalbumin-induced asthma hi mice. Methods: C57BL/6 mice were sensitized and challenged with OVA (ovalbumin) for 12 weeks (once a week) Two experimental groups were treated with different concentrations (1%, 0.1%) of Mori Folium herbal acupuncture at Chok-samni (St36) for the later 8 weeks (3times/week). Result: 1. Lung weight of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. 2. Total Leukocytes in BALE of the mice soup treated with Mori Folium herbal acupuncture decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated with Mori Folium herbal acupuncture decreased significant1y compared with that of control group. 4. The number of Gr-1+/CD11b, CCR3+, CD4+, CD8+, CD3e+/CD69+, IgE+/B220+ cells in the lung of the mice group treated with Mon Folium herbal acupuncture deceased significantly compared with that of group. 5. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with Mori Folium herbal acupuncture deceased significantly compared with that of control group. 6. The concentration of IL-4 in BALF of the mice group treated with Mori Folium herbal acupuncture decreased signifint1y compared with that of control group. Conclusion: We conclude that Mori Folium herbal acupuncture is effective on OVA-induced asthma of C57BL/6 mouse.

LPS로 유도한 RAW 264.7 세포의 염증반응에서 자초(紫草)의 항염증 효과

최선복 ( Sun Bok Choi ),배기상 ( Gi Sang Bae ),조일주 ( Il Joo Jo ),박경철 ( Kyoung Chel Park ),서승희 ( Seung Hee Seo ),김동구 ( Dong Goo Kim ),신준연 ( Joon Yeon Shin ),곽태신 ( Tae Sin Gwak ),이정현 ( Jung Hyun Lee ),이금산 ( G 대한본초학회 2013 大韓本草學會誌 Vol.28 No.2

Objective: Lithospermum Erythrorhizon (LE) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that LE aqueous extract could show the anti-inflammatory effects in RAW 264.7cells. The purpose of this study was to investigate the anti-inflammatory effect of aqueous extract from LE on lipopolysaccharide (LPS) - induced inflammatory response. Methods: To measure out the cytotoxicity of LE, we performed the MTT assay. To evaluate the anti-inflammatory effects of LE, we examined the inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-a, interleukin, (IL)-1β and (IL)-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB) activation by western blot. Results : Aqueous Extract from LE itself did not have any cytotoxic effect in RAW 264.7 cells. Aqueous extract from LE inhibited LPS-induced productions of inflammatory mediators such as NO, PGE2, and pro-inflammatory cytokines including TNF-a, IL-1β and IL-6 in RAW 264.7cells. In addition, LE inhibited the phosphorylation of p38 kinases (p38), c-Jun NH2-terminal kinase (JNK), and NF-κB activation in RAW 264.7 cells. Conclusion : LE down-regulated LPS-induced production of inflammatory mediators through the inhibition of p38, JNK and NF-κB activation. Taken together, these results could provide the evidence for the anti-inflammatory effects of LE. Therefore, LE may be a novel target in the management of inflammation and help to support a potential strategy for prevention and therapy of inflammatory diseases.