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 <i>Ureaplasma urealyticum</i> 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 <i>U. urealyticum</i> 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 <i>U. urealyticum</i> antigen (≧4 × 10⁷ 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 <i>U. urealyticum</i>. 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 <i>U. urealyticum</i> and inhibited by the steroids (p < 0.05). The expression of ICAM-1 was reduced by 85.5% when the TNF-α production was neutralized with an anti-TNF-α antibody. Our findings imply that <i>U. urealyticum </i>might be involved in the development of CLD of prematurity.

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