Induction of human macrophage vascular endothelial growth factor and intercellular adhesion molecule-1 by Ureaplasma urealyticum and downregulation by steroids.
Chronic lung disease (CLD) remains a major cause of morbidity for the prematurely born infant. The pathogenesis of CLD is complex and has not been defined entirely. Infection and lung inflammatory events have been thought to play a key role in the development of CLD. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated and steroids produce some improvement in neonates with this disease. The aim of this study was to investigate if U. urealyticum could stimulate macrophages to produce vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) in vitro, which are potentially associated with both early and later pathological changes in the lung during the development of CLD. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (>/=4 x 10(7) color-changing units/ml) stimulated human macrophages (phorbol 12-myristate 13-acetate-differentiated THP-1 cell line) to produce VEGF and soluble ICAM-1 in a dose-dependent manner (p < 0.05) measured by ELISA. Likewise, cell surface ICAM-1 (CD54) measured by flow cytometry was increased after stimulation with U. urealyticum. This effect was attenuated by budesonide and dexamethasone (p < 0.05). The mRNA expressions of VEGF and ICAM-1 detected by a semi-quantitative reverse transcriptase polymerase chain reaction were also induced in response to U. urealyticum and inhibited by the steroids (p < 0.05). The expression of ICAM-1 was reduced by 85.5% when the TNF-alpha production was neutralized with an anti-TNF-alpha antibody. Our findings imply that U. urealyticum might be involved in the development of CLD of prematurity.
Neonatal Unit, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden. ying-hua.li@kbh.ki.se
Ying-Hua
YH
Li
Annelie
A
Brauner
Jørgen Skov
JS
Jensen
Kjell
K
Tullus
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008171:Lung Diseases / Q000382:microbiology; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D016869:Ureaplasma Infections / Q000378:metabolism* / Q000382:microbiology; D016990:Ureaplasma urealyticum / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D000942:Antigens, Bacterial; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018799:Intercellular Adhesion Molecule-1; D019819:Budesonide; D003907:Dexamethasone