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dc.contributor.authorWang, B. N.zh_CN
dc.contributor.authorLim, D. J.zh_CN
dc.contributor.authorHan, J. H.zh_CN
dc.contributor.authorKim, Y. S.zh_CN
dc.contributor.authorBasbaum, C. B.zh_CN
dc.contributor.authorLi, J. D.zh_CN
dc.contributor.author韩家淮zh_CN
dc.date.accessioned2013-12-12T02:24:44Z
dc.date.available2013-12-12T02:24:44Z
dc.date.issued2002zh_CN
dc.identifier.citationJournal of Biological Chemistry,277(2):949-957zh_CN
dc.identifier.issn0021-9258zh_CN
dc.identifier.otherISI:000173166800013zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65848
dc.description.abstractNontypeable Haemophilus influenzae (NTHi) is an important human pathogen that causes chronic otitis media with effusion (COME) in children and exacerbation of chronic obstructive pulmonary disease (COPD) in adults. Mucin overproduction, a hallmark of both diseases, has been shown to directly cause conductive hearing loss in COME and airway obstruction in COPD. The molecular mechanisms underlying mucin overproduction in NTHi infections still remain unclear. Here, we show that NTHi strongly up-regulates MUC5AC mucin transcription only after bacterial cell disruption. Maximal up-regulation is induced by heat-stable bacterial cytoplasmic proteins, whereas NTHi surface membrane proteins induce only moderate MUC5AC transcription. These results demonstrate an important role for cytoplasmic molecules from lysed bacteria in the pathogenesis of NTHi infections, and may well explain why many patients still have persistent symptoms such as middle ear effusion in COME after intensive antibiotic treatment. Furthermore, our results indicate that activation of p38 mitogen-activated protein kinase is required for NTHi-induced MUC5AC transcription, whereas activation of phosphoinositide 3-kinase-Akt pathway leads to down-regulation of NTHi-induced MUC5AC transcription via a negative cross-talk with p38 mitogen-activated protein kinase pathway. These studies may bring new insights into molecular pathogenesis of NTHi infections and lead to novel therapeutic intervention for COME and COPD.zh_CN
dc.language.isoen_USzh_CN
dc.subjectNF-KAPPA-Bzh_CN
dc.subjectMIDDLE-EAR EFFUSIONSzh_CN
dc.subjectPSEUDOMONAS-AERUGINOSAzh_CN
dc.subjectOTITIS-MEDIAzh_CN
dc.subjectHEMOPHILUS-INFLUENZAEzh_CN
dc.subjectSIGNALING PATHWAYSzh_CN
dc.subjectRESPIRATORY MUCINSzh_CN
dc.subjectEPITHELIAL-CELLSzh_CN
dc.subjectPATHOGENESISzh_CN
dc.subjectDISEASEzh_CN
dc.titleNovel cytoplasmic proteins of nontypeable Haemophilus influenzae up-regulate human MUC5AC mucin transcription via a positive p38 mitogen-activated protein kinase pathway and a negative phosphoinositide 3-kinase-Akt pathwayzh_CN
dc.typeArticlezh_CN


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