Type

Journal Article

Authors

N G McElvaney
S J O'Neill
R Coakley
C P Rooney
C C Taggart
G Meachery
C M Greene

Subjects

Biochemistry

Topics
blood interleukin 18 receptor alpha subunit male biosynthesis lymphocyte activation pathology physiology middle aged interleukin 18 transcriptional activation nf kappa b receptors interleukin cd4 positive t lymphocytes interleukin 2 epithelium th1 cells u937 cells receptors interleukin 18 humans transcription factor ap 1 cytokines adult sarcoidosis pulmonary gene expression regulation female jurkat cells immunology genetics metabolism bronchoalveolar lavage fluid il18r1 protein human

Role of IL-18 in CD4+ T lymphocyte activation in sarcoidosis. (2000)

Abstract Sarcoidosis is a granulomatous disease of unknown etiology associated with the expansion of IL-2-producing activated CD4(+) T lymphocytes. A number of factors including the recently described IL-18 have been implicated in IL-2 expression in vitro. We investigated the role of IL-18 in IL-2 expression in sarcoidosis. Eighteen individuals with sarcoidosis and 15 normal controls were studied. IL-18R expression and epithelial lining fluid (ELF) concentrations of IL-18 were significantly elevated in the sarcoid group (p = 0.0143 and 0.0024, respectively). Both AP1 and NF-kappaB, transcription factors that regulate IL-2 gene expression, were activated in vivo in sarcoid pulmonary CD4(+) T lymphocytes. Transcription factor activity was not detected in pulmonary CD4(+) T lymphocytes from normal controls or from peripheral blood CD4(+) T lymphocytes from individuals with sarcoidosis, further evidence of compartmentalization of the lymphoproliferative process in this condition. We examined the effects of IL-18 on AP1 and NF-kappaB in Jurkat T cells in vitro. These effects were both time and dose dependent. Examination of transcription factor activation and IL-2 gene expression in Jurkat T cells revealed that sarcoid but not normal ELF activated AP1 and NF-kappaB, induced IL-2 gene transcription, and up-regulated IL-2 protein production. Addition of IL-18 to normal ELF also induced IL-2 mRNA accumulation, whereas correspondent depletion of IL-18 from sarcoid ELF using neutralizing Abs abrogated all of the effects. These data strongly implicate IL-18 in the pathogenesis of sarcoidosis via activation of AP1 and NF-kappaB, leading to enhanced IL-2 gene expression and IL-2 protein production and concomitant T cell activation.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

N G McElvaney, S J O'Neill, R Coakley, C P Rooney, C C Taggart, G Meachery, C M Greene

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150