Chlamydophila pneumoniae triggers release of CCL20 and vascular endothelial growth factor from human bronchial epithelial cells through enhanced intracellular oxidative stress and MAPK activation.
BACKGROUND
Chlamydophila pneumoniae may contribute to the pathogenesis of asthmatic airway inflammation through chemical mediators secreted by C. pneumoniae-infected bronchial epithelial cells (BECs). Recently, CCL20 and vascular endothelial growth factor (VEGF) were reported to be released from BECs and to play a role in the pathogenesis of asthma.


OBJECTIVE
To determine if C. pneumoniae infection of BECs induces the secretion of CCL20 and VEGF, we measured that by ELISA in human BECs infected with C. pneumoniae. Transcripts of CCL20 and VEGF were assayed by semi-quantitative RT-PCR. To investigate the underlying mechanism, the activation of MAPK and intracellular reactive oxygen species (ROS) in these C. pneumoniae-infected BECs was measured, as well as the effects of inhibitors of MAPK and ROS on CCL20 and VEGF expression.


RESULTS
Compared with non-infected BECs, C. pneumoniae-infected BECs showed enhanced secretion of CCL20 and VEGF. C. pneumoniae-infected BECs also showed enhanced intracellular ROS and an increased ratio of phosphorylated to non-phosphorylated p38. Inhibition of p38 suppressed CCL20 and VEGF secretion, as did a NADPH oxidase blocker and an antioxidant, in C. pneumoniae-infected BECs.


CONCLUSIONS
C. pneumoniae infection of BECs may play a role in the pathogenesis of asthma through the enhanced production of CCL20 and VEGF. The association between increased cytokine production and increased intracellular ROS suggests that antioxidants may benefit asthmatics in selected situations.
Kim
Tae-Bum
TB
Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, South Korea.
Moon
Keun-Ae
KA
Lee
Ki-Young
KY
Park
Chan-Sun
CS
Bae
Yun-Jeong
YJ
Moon
Hee-Bom
HB
Cho
You Sook
YS
D000975:Antioxidants / Q000494:pharmacology; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D023521:Chlamydophila Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009249:NADP / Q000037:antagonists & inhibitors; D009861:Onium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D054418:Chemokine CCL20; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D009249:NADP; C007517:diphenyleneiodonium; D048051:p38 Mitogen-Activated Protein Kinases