scholarly journals The Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Induces the Inflammatory Factor Interleukin-8 following Chlamydia trachomatis Infection

2007 ◽  
Vol 75 (12) ◽  
pp. 5924-5929 ◽  
Author(s):  
Kerry R. Buchholz ◽  
Richard S. Stephens
Keyword(s):  
Protein Kinase ◽  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Interleukin 8 ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factor ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Diseases associated with Chlamydia infection, such as pelvic inflammatory disease and ectopic pregnancy, are due to inflammation-mediated tissue damage and scarring that occur after chronic or repeated infections. The inflammatory chemokine interleukin-8 (IL-8) is produced by Chlamydia-infected cells through an endogenous mechanism of activation, independent of soluble factors in the supernatant. The host signaling pathways necessary for this response are not understood, but the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) has been shown to be activated at similar times as IL-8 mRNA up-regulation. The purpose of this study was to elucidate the MAPK pathways necessary to induce the endogenous IL-8 response to Chlamydia trachomatis infection of epithelial cells. IL-8 induced by infection with C. trachomatis L2 was shown to be dependent on ERK and independent of p38 and Jun N-terminal MAPK by use of chemical inhibitors of the signaling pathways. Persistent ERK activation during IL-8 mRNA production at 24 h postinfection was necessary to maintain the response. C. trachomatis serovar D also induced IL-8 in an ERK-dependent manner. We concluded that IL-8 induced during infection of epithelial cells is dependent on continual activation of ERK by C. trachomatis.

scholarly journals Up-Regulation of Interleukin-8 by Novel Small Cytoplasmic Molecules of Nontypeable Haemophilus influenzae via p38 and Extracellular Signal-Regulated Kinase Pathways

2003 ◽  
Vol 71 (10) ◽  
pp. 5523-5530 ◽  
Author(s):  
Beinan Wang ◽  
P. Patrick Cleary ◽  
Haidong Xu ◽  
Jian-Dong Li
Keyword(s):  
Protein Kinase ◽  
Haemophilus Influenzae ◽  
Intracellular Signaling ◽  
Interleukin 8 ◽  
Mitogen Activated Protein Kinase ◽  
Akt Pathway ◽  
Chronic Obstructive ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

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 ≤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.

Sign in / Sign up

Export Citation Format

Share Document