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| 1 | Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33:implications for allergic inflammation显示文摘The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophilia,IgE secretion and hypertrophy of airway epithelium in mice.In the present study,we characterized the activation of human eosinophils by IL-33,and investigated the underlying intracellular signaling mechanisms.IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule(ICAM)-1 on eosinophils,but it suppressed that of ICAM-3 and L-selectin.In addition,IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2.We found that IL33-mediated enhancement of survival,induction of adhesion molecules,and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor(NF)-KB,p38 mitogen-activated protein kinase(MAPK)and extracellular signal-regulated kinase(ERK)pathways.Furthermore,we compared the above IL-33 activities with two structurally and functionally related cytokines,IL-1 B and IL-18.IL-1β,but not IL-18,markedly upregulated cell surface expression of ICAM-1.IL-1βand IL-18 also significantly enhanced eosinophil survival,and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB,p38 MAPK and ERK pathways.Synergistic efects on the release of IL-6 were also observed in combined treatment withIL-1B,IL-18 and IL-33.Taken together,our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation. | Joyce YS Chow Chun K Wong Phyllis FY Cheung Christopher WK Lam | 2010 | Cellular & Molecular Immunology2010，7，1： | 22 |
| 2 | Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis显示文摘Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune responses.However,the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes(FLS)in rheumatoid arthritis(RA)have not been elucidated.Therefore,we investigated the in vitro effects of monosodium urate crystals,alone or in combination with the inflammatory cytokines tumor-necrosis factor(TNF)-a or interleukin(IL)-1b,on the activation of human FLS from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these crystals.Monosodium urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6,the chemokine CXCL8 and the matrix metalloproteinase(MMP)-1 from both normal and RA-FLS(all P,0.05).Moreover,the additive or synergistic effect on the release of IL-6,CXCL8 and MMP-1 from both normal and RA-FLS was observed following the combined treatment with monosodium urate crystals and TNF-a or IL-1b.Further experiments showed that the release of the measured inflammatory cytokine,chemokine and MMP-1 stimulated by monosodium urate crystals were differentially regulated by the intracellular activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways but not the p38 mitogen-activated protein kinase pathway.Our results therefore provide a new insight into the uric acid crystal-activated immunopathological mechanisms mediated by distinct intracellular signal transduction pathways leading to joint inflammation in RA. | Da P Chen Chun K Wong Lai S Tam Edmund K Li Christopher WK Lam | 2011 | Cellular & Molecular Immunology2011，8，6： | 5 |
| 3 | IL-3,5 and GM-CSF-induced adhesion molecule expression on eosinophils by p38 MAPK and NF-κB显示文摘 | Wong CK Ip WK Lam CWK | 2003 | Am J Respir Cell Mol Biol2003，29，： | 1 |
| 4 | Primary hepatolithiasis, re- current pyogenic cholangitis, and oriental cholangiohepatitis: a tale of 3 countries 显示文摘 | Tsui WM Lam PW Lee WK | 2011 | Adv Anat Pathol2011，18，4： | 1 |
| 5 | Neonatal narcotics withdrawal in HongKong Chinese 显示文摘 | Lam SK To WK | 1994 | Asia Oceania J Obstet Gynecol1994，20，： | 1 |
| 6 | Hypophysitis presented as inflammatory pseudotumor in immunoglobulin G4-related systemic disease显示文摘 | Wong S Lam WY Wong WK | 2007 | Hum Pathol2007，38，11： | 1 |
| 7 | Hepatic cryosurgery for recurrent hepatocellular catcinoma after hepatectomy:a preliminary report显示文摘 | Lam CM Yuen WK Fan ST | 1998 | J Surg Oncol1998，68，： | 1 |
| 8 | Current antiviral therapy of chronic hepatitis B: efficacy and safety显示文摘 | Lam YF Yuen MF Seto WK | 2011 | Curt Hepat Rep2011，10，4： | 1 |
| 9 | Thyroid dysfunction in laryngectomees- 10 years after treatment显示文摘 | Ho AC Ho WK Lam PK | 2008 | Head Neck2008，30，3： | 1 |
| 10 | Resilience in the year after cancer diagnosis a cross-lagged panel analysis of the reciprocity between psycho- logical distress and well-being 显示文摘 | Hou WK Lam JH | 2014 | J Behav Med2014，37，3： | 1 |
| 11 | Overexpression of matrix metalloproteinase-8 and 9 in bronchiectatic airways in vivo显示文摘 | Zheng L Lam WK Tipoe GL et a1 | 2002 | Eur Respir J2002，20，1： | 1 |
| 12 | Neonatal narcotics withdrawal in Hong Kong Chinese显示文摘 | To WK | 1994 | Asia Oceania J Obstet Gynaecol1994，20，3： | 1 |
| 13 | Hypophysitis presented as inflammatory pseudotumor in immunaglobulin G4-related systemic disease显示文摘 | Wong S Lam WY Wong WK | 2007 | Hum Pathol2007，38，11： | 1 |
| 14 | Helicobacter pylori sero-prev-alence in asthma显示文摘 | Tsang KW Lam WK Chan KN | 2000 | Respir Med2000，，94： | 1 |
| 15 | Respiratory problems in myasthenia gravis显示文摘 | Ip MS So SY Lam WK | 1985 | Ann Acad Med Singapore1985，14，3： | 1 |
| 16 | Endobronchial tuberculosis revisited显示文摘 | Ip Ms So SY Lam WK Mok CK | 1986 | Chest1986，5，： | 1 |
| 17 | Rapid diagnosis of suspected pulmonary tuberculosis by fiberoptic bronchoscopy显示文摘 | So SY Lam WK Yu DYL | 1982 | Tubercle1982，63，： | 1 |
| 18 | Fiberoptic bronchoscopy in the diagnosis of bronchial cancer:comparison of washings,brushings and biopsies in central and peripheral tumors显示文摘 | Lam WK So SY Hsu C | 1983 | Clin Oncol1983，9，： | 1 |
| 19 | Endobronchial tuberculosis revisited显示文摘 | Ip Ms So SY Lam WK Mok CK | 1986 | Chest1986，5，： | 1 |
| 20 | Regression of high-grade gastric mucosaassociated iymphoid tissue lymphoma with Helicobacter pylori after triple antibiotic therapy显示文摘 | Ng WW Lam CP Chau WK | 2000 | Gastrointest Endosc2000，51，1： | 1 |
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