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Ureaplasma urealyticum-induced production of proinflammatory cytokines by macrophages
1Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden.
Abstract:
Ureaplasma urealyticum is relatively common in the respiratory tract of very low birth weight infants and has been hypothesized to be involved in the development of chronic lung disease. The purpose of this study was to investigate whether U. urealyticum could stimulate macrophages to produce proinflammatory cytokines in vitro, which are early pathologic changes in the lung during the development of chronic lung disease. A human monocytic cell line (THP-1) differentiated to macrophages, a rat alveolar macrophage cell line (Nr8383), and human lung macrophages from tracheobronchial aspirate fluid in preterm infants were exposed to U. urealyticum antigen for 24 h. The protein levels of human IL-6, tumor necrosis factor-alpha (TNF-alpha), and rat TNF-alpha were measured with ELISA. Rat IL-6 was analyzed with a specific bioassay. The mRNA levels of these cytokines were detected by reverse transcriptase-PCR. The production of TNF-alpha and IL-6 increased after stimulation with U. urealyticum in both the human and rat macrophage cell lines. In tracheobronchial aspirate fluid macrophages, U. urealyticum increased the production of TNF-alpha from 14 to 84% and IL-6 from 46 to 268% above control levels. U. urealyticum also induced gene expression of TNF-alpha and IL-6. In conclusion, U. urealyticum could be an important factor in the development of chronic lung disease because of its ability to induce alveolar macrophage proinflammatory cytokine production.
Insights
Ureaplasma urealyticum infection in preterm infants may contribute to chronic lung disease by triggering macrophages to release inflammatory cytokines. This study demonstrates U. urealyticum
Area of Science:
- Neonatal respiratory health
- Microbiology and immunology
- Inflammatory disease mechanisms
Background:
- Ureaplasma urealyticum is frequently found in the respiratory tracts of very low birth weight infants.
- This bacterium is suspected to play a role in the pathogenesis of chronic lung disease (CLD).
- Proinflammatory cytokines are key early indicators in lung pathology during CLD development.
Purpose of the Study:
- To determine if Ureaplasma urealyticum can stimulate macrophages to produce proinflammatory cytokines in vitro.
- To investigate the role of U. urealyticum in the early stages of chronic lung disease development.
Main Methods:
- Human (THP-1) and rat (Nr8383) macrophage cell lines, plus primary human infant macrophages, were exposed to U. urealyticum antigen.
- Cytokine protein levels (IL-6, TNF-alpha) were measured using ELISA and bioassays.
- Cytokine gene expression (mRNA) was analyzed via reverse transcriptase-PCR.
Main Results:
- U. urealyticum stimulation significantly increased TNF-alpha and IL-6 production in both human and rat macrophage cell lines.
- In infant macrophages, U. urealyticum elevated TNF-alpha by 14-84% and IL-6 by 46-268%.
- U. urealyticum also induced the gene expression of TNF-alpha and IL-6 in macrophages.
Conclusions:
- Ureaplasma urealyticum possesses the capacity to induce proinflammatory cytokine production by alveolar macrophages.
- This cytokine-inducing ability suggests U. urealyticum is a significant factor in the development of chronic lung disease in vulnerable infants.