Activation of Nuclear Factor-κB and Its Suppression by Dexamethasone in Polymorphonuclear Leukocytes: Newborn Versus Adult
| Autor: | Dennis Davidson, Ivana Vancurova, Patricia Bellani |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
medicine.medical_specialty P50 Neutrophils Neutrophile In Vitro Techniques Dexamethasone Proinflammatory cytokine Internal medicine medicine Humans Electrophoretic mobility shift assay Transcription factor DNA Primers Base Sequence business.industry Infant Newborn NF-kappa B Endocrinology Cord blood Pediatrics Perinatology and Child Health Immunology Tumor necrosis factor alpha business medicine.drug |
| Zdroj: | Pediatric Research. 49:257-262 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/00006450-200102000-00021 |
| Popis: | Polymorphonuclear leukocytes (PMN) of the newborn, to a greater extent than those of the adult, have the ability to amplify PMN recruitment to an inflammatory site by their own release of IL-8, and this process is inhibited by dexamethasone. The aim of the present study was to determine whether the regulation of nuclear factor-kappaB (NF-kappaB) could explain the previous observations. NF-kappaB is a transcription factor pivotal for expression of genes encoding inflammatory cytokines such as IL-8, but NF-kappaB has not been previously studied in the PMN of the newborn. NF-kappaB activation was measured by an electrophoretic mobility shift assay in nuclear extracts prepared from PMN isolated from adults and cord blood from newborns. Two distinct molecular forms of NF-kappaB were identified after tumor necrosis factor-alpha stimulation; this included the previously characterized p50/65 heterodimer and a newly identified p50/50 homodimer. Both NF-kappaB dimers were activated by tumor necrosis factor-alpha to significantly higher levels in the neutrophil of the newborn versus adult. An additional new finding was that pretreatment of PMN with dexamethasone (10(-7) M, therapeutic range) inhibited activation of both NF-kappaB complexes in both the newborn and the adult PMN. We conclude that the increased activation of NF-kappaB by the PMN of the newborn may play an important role in neonatal inflammatory reactions. Eventually, specific targeting of NF-kappaB activation in the neutrophil may be an effective molecular approach for the treatment of neutrophil-mediated disorders in the newborn. |
| Databáze: | OpenAIRE |
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