Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase byUreaplasma urealyticumin Macrophages

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Abstract
Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticumin the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability ofU. urealyticumto stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth ofU. urealyticumwas also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found thatU. urealyticumantigen (≥4 × 107color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent 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 (10−4to 10−6M) (P< 0.05). The mRNA and protein levels of iNOS were also induced in response toU. urealyticumand inhibited by steroids.U. urealyticumantigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced byU. urealyticumcaused a sixfold reduction of its own growth after infection for 10 h. Our findings imply thatU. urealyticummay be an important factor in the development of CLD. The host defense response againstU. urealyticuminfection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

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