Activation of nuclear factor kappa B and induction of inducible nitric oxide synthase by Ureaplasma urealyticum in macrophages

Chronic lung disease (CLD) of prematurity is an inflammatory disease,vith a multifactorial etiology. The importance of Ureaplasma urealyticum in the d evelopment of CLD is debated, and steroids produce some improvement in neon ates with this disease. In the present study, the capability of U. urealyti cum to stimulate rat alveolar macrophages to produce nitric oxide (NO), exp ress inducible nitric oxide synthase (iNOS), and activate nuclear factor ka ppaB (NF-kappaB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexame thasone and budesonide on these processes was examined. We found that U. ur ealyticum antigen (greater than or equal to4 x 10(7) color-changing units/m l) stimulated alveolar macrophages to produce NO in a dose- and time-depend ent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone ( 10(-4) to 10(-6) M) (P < 0.05). The mRNA and protein levels of iNOS were al so induced in response to U. urealyticum and inhibited by steroids. U. urea lyticum antigen triggered NF-<kappa>B activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induc ed by U. urealyticum caused a sixfold reduction of its own growth after inf ection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response against U. ure alyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-kappaB activation, iNOS expression, and NO production mi ght partly explain the beneficial effect of steroids in neonates with CLD.