Abstract:
:Nontypeable Haemophilus influenzae (NTHI) is an important etiological agent of otitis media (OM) and of exacerbated chronic obstructive pulmonary diseases (COPD). Inflammation is a hallmark of both diseases. Interleukin-8 (IL-8), one of the important inflammatory mediators, is induced by NTHI and may play a significant role in the pathogenesis of these diseases. Our studies demonstrated that a soluble cytoplasmic fraction (SCF) from NTHI induced much greater IL-8 expression by human epithelial cells than did NTHI lipooligosaccharides and envelope proteins. The IL-8-inducing activity was associated with molecules of < or =3 kDa from SCF and was peptidase and lipase sensitive, suggesting that small lipopeptides are responsible for the strong IL-8 induction. Moreover, multiple intracellular signaling pathways were activated in response to cytoplasmic molecules. The results indicated that the p38 mitogen-activated protein kinase (MAPK) and Src-dependent Raf-1-Mek1/2-extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) pathways are required for NTHI-induced IL-8 production. In contrast, the phosphatidylinositol 3-kinase (PI3K)-Akt pathway did not affect IL-8 expression, although this pathway was concomitantly activated upon exposure to NTHI SCF. The PI3K-Akt pathway was also directly activated by IL-8 and significantly inhibited by an antagonist of IL-8 receptors during NTHI stimulation. These results indicated that the PI3K-Akt pathway is activated in response to IL-8 that is induced by NTHI and may lead to other important epithelial cell responses. This work provides insight into essential molecular and cellular events that may impact on the pathogenesis of OM and COPD and identifies rational targets for anti-inflammatory intervention.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Wang B,Cleary PP,Xu H,Li JDdoi
10.1128/iai.71.10.5523-5530.2003keywords:
subject
Has Abstractpub_date
2003-10-01 00:00:00pages
5523-30issue
10eissn
0019-9567issn
1098-5522journal_volume
71pub_type
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1974-04-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.01249-09
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.26.2.402-407.1979
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journal_title:Infection and immunity
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更新日期:2004-03-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2002-04-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1992-03-01 00:00:00