Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increase in the ratio of memory to naive T cells has been postulated to underlie immune hyporesponsiveness accompanying aging. Our analyses of the induction of nuclear factor-kappaB (NFkappaB) in activated memory (CD45RO+) and naive (CD45RA+) T cell subsets from young and elderly donors has demonstrated that, regardless of donor age, memory T cells are not significantly altered in their responsiveness to TNF-alpha-mediated induction of NFkappaB. Although treatment with TNF-alpha induced nuclear localization of NFkappaB in both memory and naive T cell subsets, irrespective of the age of the donor, the levels of induced NFkappaB were significantly lower in both subsets of T cells obtained from the elderly, when compared to those in young. Examination of IkappaB alpha regulation revealed that TNF-alpha-mediated degradation of IkappaB alpha in both memory and naive T cells from the elderly was severely impaired, thus contributing to the lowered induction of the observed NFkappaB. In addition, this age-related decrease in induction of nuclear NFkappaB correlated with decrease in intracellular IL-2 receptor expression and anti-CD3-induced proliferation of both memory and naive T cells subsets. Taken together, our results suggest that the age-related hyporesponsiveness cannot be attributed to a skewing of the T cell population towards a memory phenotype in the elderly.
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PMID:Nuclear factor-kappaB induction in CD45RO+ and CD45RA+ T cell subsets during aging. 972 Jun 48

In the CNS, the transcription factor NF-kappaB is a key regulator of inflammation and secondary injury processes. Following trauma or disease, the expression of NF-kappaB-dependent genes is activated, leading to both protective and detrimental effects. In this study, we show that transgenic inactivation of astroglial NF-kappaB (glial fibrillary acidic protein-IkappaB alpha-dominant-negative mice) resulted in reduced disease severity and improved functional recovery following experimental autoimmune encephalomyelitis. At the chronic stage of the disease, transgenic mice exhibited an overall higher presence of leukocytes in spinal cord and brain, and a markedly higher percentage of CD8(+)CD122(+) T regulatory cells compared with wild type, which correlated with the timing of clinical recovery. We also observed that expression of proinflammatory genes in both spinal cord and cerebellum was delayed and reduced, whereas the loss of neuronal-specific molecules essential for synaptic transmission was limited compared with wild-type mice. Furthermore, death of retinal ganglion cells in affected retinas was almost abolished, suggesting the activation of neuroprotective mechanisms. Our data indicate that inhibiting NF-kappaB in astrocytes results in neuroprotective effects following experimental autoimmune encephalomyelitis, directly implicating astrocytes in the pathophysiology of this disease.
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PMID:Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. 1923 57