Type

Journal Article

Authors

Noel G McElvaney
Shane J O'Neill
Clifford C Taggart
Paula M Gallagher
Michael O'Mahony
Gerard Meachery
Catherine M Greene
Deirdre M Kelly

Subjects

Microbiology

Topics
rna ribosomal 16s male sarcoidosis pulmonary adult physiopathology interleukin 18 humans physiology pharmacology female t lymphocytes helper inducer microbiology tuberculin bronchoalveolar lavage fluid gram negative bacteria lipopolysaccharides up regulation

Endotoxin up-regulates interleukin-18: potential role for gram-negative colonization in sarcoidosis. (2005)

Abstract Sarcoidosis is a granulomatous disease of unknown etiology characterized by a helper T-cell type 1-mediated process. Previously we demonstrated a role for interleukin-18 in sarcoidosis. Here we examine the regulation of interleukin-18 in this condition. Cytokine levels in sarcoid epithelial lining fluid were measured by ELISA. We examined interleukin-18 promoter activity and mRNA and protein levels in the epithelial lining fluid of individuals with active sarcoidosis, and of individuals recovered from sarcoidosis, in response to purified protein derivative of Mycobacterium tuberculosis, beryllium sulfate, zirconium sulfate, aluminum sulfate, and lipopolysaccharide. Endotoxin levels in the epithelial lining fluid of individuals with sarcoidosis, individuals recovered from sarcoidosis, and control subjects were assessed by Limulus amebocyte lysate analysis. Allele-specific polymerase chain reaction was used to genotype 94 patients with sarcoidosis and 97 control subjects for the interleukin-18 -607(A/C) polymorphism. Species-specific polymerase chain reaction identified bacterial DNA in fluid samples. Epithelial lining fluid from active sarcoids contained elevated levels of interleukin-18, interferon-gamma, and interleukin-12 compared with recovered patients and also contained significantly higher levels of endotoxin. Depletion of endotoxin from this epithelial lining fluid reduced its effect on the human interleukin-18 promoter in vitro. There was a higher frequency of the -607C allele and -607(C/C) genotype in the sarcoidosis population compared with control subjects; however, this was not associated with a functional response to endotoxin treatment. Finally, bacterial 16S rRNA from Haemophilus influenzae and Moraxella catarrhalis was detected in sarcoid fluid samples. The pathogenesis of sarcoidosis is propagated through the actions of a helper T-cell type 1-driven response. This study shows that gram-negative bacteria may contribute to this effect by upregulating interleukin-18 expression.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Shane J O'Neill, Clifford C Taggart, Paula M Gallagher, Michael O'Mahony, Gerard Meachery, Catherine M Greene, Deirdre M Kelly

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