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김창근,Hirohito Kita,유진호,유영,고영률,김병의 대한천식알레르기학회 2004 천식 및 알레르기 Vol.24 No.4
Background and Objective: Previous studies, during acute asthma exacerbations, have suggested roles for the Th2 cytokines in promoting airway inflammation in asthma patients. We assessed mediators of airway inflammation during the chronic asymptomatic phase of asthma. Method: Nine nonatopic asthma (NAA) patients, 15 atopic asthma (AA) patients, 15 atopic controls (AC), and 21 normal controls (NC) underwent sputum induction in asymptomatic phase. Sputum total cell counts and differentials were determined. Levels of the cytokines, IL-4, IL-5, GM-CSF, IFN-γ were measured by ELISA. Result: NAA and AA patients showed a higher percentage of sputum eosinophils compared to AC (P<0.001, P<0.01, respectively) and NC (P<0.001); furthermore, NAA patients showed higher percentage of sputum eosinophils and total eosinophils compared to AA (P<0.01, P=0.001, respectively). No differences were observed in the sputum levels of IL-4 and IL-5 among the four groups. In contrast, the IFN-γ levels were higher in NAA (P<0.001) and AA (P<0.001) patients compared to AC and NC. Interestingly, the GM-CSF levels were higher in AA patients compared to AC (P=0.01) or NC (P<0.001). In NAA, AA, and AC patients, the percentage of sputum eosinophils and total eosonphils correlated positively with the levels of IFN-γ (Rs=0.643 and P<0.001, Rs=0.580 and P<0.001), GM-CSF (Rs=0.459 and P<0.01, Rs=0.394 and P<0.05), but not with the IL-5 levels. Conclusions: The baseline airway inflammation of asthma, irrespective of an atopic or nonatopic diathesis, is characterized by eosinophilic inflammation and a Th1 cytokine, IFN-γ. GM-CSF, instead of IL-5 may have a role in airway eosinophilia during the chronic phase of asthma.
기도 내 호산구성 염증에서 IL-5와 Eotaxin의 역할
김창근,Kita, Hirohito,유진호,고영률 대한천식 및 알레르기학회 2004 천식 및 알레르기 Vol.24 No.1
Background : IL-5 and eotaxin are the most important cytokines/chemokines responsible for regulating eosinophil locomotion. Objrctive : We investigated the role of IL-5 and eotaxin in airway eosinphilic inflammation in patients with chronic cough by analyzing suptum from patients. Methods : Thirty-one patients who had chronic cough and seven normal control subjects were enrolled. Patients were divided into two groups, asthma group (n=15) and non-asthma group (n=16). Sputum was induced by inhalation of hypertonic saline. Total cell counts and differentials were determined. The levels of IL-5 and eotaxin were measured by ELISA. and the levels of EDN and MBP were measured by RIA. Results : Patients in the asthma group showed higher percentage of eosinophils and higher levels of EDN and IL-5 (F<.001, F<.05 and F<.05, respectively) compared subjects in the control group and higher % eosinephils, higher levels of EDN and MBP (F<.001, F<.05 and F<.05, respectively) compared to subjects in the control group. Non-asthma group patients also showed higher percentage of eosinophils and increased IL-5 levels (F<.05 and F<.05. respectively) compared to the control group. The eotaxin level correlated positively with percentage of eosinophils (Rs=0.60. F<.001), the EDN (Rs=0.59, F<.001) and MBP (Rs=0.73, F<.01) levels and correlated inversely with FEV1% pred. (Rs=-0.71, F<.01). Unexpectedly, the IL-5 levels did not correlate significantly with any of sputum eosinophil indices or FEV1% pred. Conclusion : Good correlation of eotaxin with sputum eosinophil indices or pulmonary function and no correlation of IL-5 with them suggest that eotaxin may play a more important role in the specific recruitment and degranulation of airway eosinophils, although both IL-5 and eotaxin are involved in local eosinophilic inflammation. (J Asthma Allergy Clin Immunol 24 : 127-36, 2004)
신승헌,김정규,Kita Hirohito 대한이비인후과학회 2004 대한이비인후과학회지 두경부외과학 Vol.47 No.6
Background and Objectives:Allergic fungal sinusitis is characterized by allergic mucin which includes eosinophils and fungal the pathophysiologic function of eosinophils by directly stimulating eosinophils with fungal antigens. Subjects and Method:Eosinophils were isolated from healthy volunters and stimulated with extracts from 5 comon fungal species (Alternaria, Aspergilus, Candida, Cladosporium, and Penicillium). Superoxide production and eosinophil derived neurotoxin (EDN) were measured to determine whether fungi activated eosinophils. An inhibition study was done using serine and cystein protease inhibitors. :When cultured with fungal antigens, eosinophils produced superoxide by Alternaria and Cladosporium but only Alternaria induced EDN production. Serine protease inhibitors (PMSF, Pefabloc) and heat treatment of fungi significantly inhibited the activation of eosinophils but the cystein protease inhibitor (E-64) wasnt inhibited. Conclusion:Eosinophils are directly activated by Alternariamay activate eosinophils which play important roles in the pathogenesis of AFS, resulting in the destruction of fungi and respiratory epithelial cells.
Shin, Myeong Heon,Lee, Young-Ah,Bae, Yoe-Sik,Kita, Hirohito,Kim, Youngdong,Ryu, Sung Ho S. Karger AG 2005 International archives of allergy and immunology Vol.137 No.suppl1
<P><I>Background:</I> Eosinophils play a key role in allergic inflammation and parasitic infections. The synthetic peptide, Trp-Lys-Tyr-Met-Val-<I>D</I>-Met (WKYMVm), has been previously shown to activate eosinophils and thus to enhance respiratory burst through the formyl peptide receptors. <I>Objective:</I> This study was undertaken to determine the intracellular signaling pathway involved in WKYMVm-stimulated superoxide production by human eosinophils. <I>Methods:</I> Purified eosinophils from peripheral blood were stimulated with various concentrations (10<SUP>-3</SUP> to 10 μ<I>M</I>) of WKYMVm and the involvement of PI3-kinase and MAP kinases in WKYMVm-triggered superoxide production was investigated using pharmacological inhibitors. <I>Results:</I> WKYMVm-induced superoxide production by eosinophils was strongly inhibited by pretreatment with the PI3-kinase inhibitor LY294002. In addition, pretreatment with the ERK1/2 kinase inhibitor PD98059 resulted in marked inhibition of superoxide production induced by WKYMVm. Indeed, WKYMVm strongly induced phosphorylation of ERK1/2. The ERK1/2 activation by the peptide was transient and peaked after 2 min of stimulation. Furthermore, ERK1/2 activation by WKYMVm was completely inhibited by pretreatment with the PI3-kinase inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220. <I>Conclusion:</I> These results suggest that WKYMVm stimulates human eosinophils to induce superoxide production via a PI3-kinase-mediated ERK1/2 pathway.</P><P>Copyright © 2005 S. Karger AG, Basel</P>