The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus.

The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Research Abstract Details 

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The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Abstract Text:

Kathleen E Sullivan,April Suriano,Kelly Dietzmann,Janice Lin,Daniel Goldman,Michelle A Petri,Kathleen E Sullivan,April Suriano,Kelly Dietzmann,Janice Lin,Daniel Goldman,Michelle A Petri,

In systemic lupus erythematosus, TNFalpha is elevated in the serum and correlates with disease activity and triglyceride levels. The stimuli that drive TNFalpha in this setting are incompletely understood. This study was designed to evaluate monocyte chromatin at the TNFalpha locus to identify semi-permanent changes that might play a role in altered expression of TNFalpha. SLE patients with relatively quiescent disease (mean Physician Global Assessment=0.6) and healthy controls were recruited for this study. TNFalpha expression was measured by intracellular cytokine staining of different monocyte subsets in patients (n=24) and controls (n=12). Histone acetylation at the TNFalpha locus was measured by chromatin immunoprecipitation using a normalized quantitative PCR in patients (n=46) and controls (n=24). There were no differences in the overall fractions of cells expressing CD14 in SLE patients compared to controls; however, the fraction of DR+/CD16+ cells expressing CD14 was slightly higher as was true in the monocyte subset defined by DR+/CD11b+. Within the monocyte population defined by physical characteristics and DR+/CD14+, TNFalpha expressing cells were more frequent in SLE patients compared to controls. Both the fraction of positive cells and the mean fluorescence intensity were higher in patients than controls. Consistent with this was the finding that monocytes from patients had increased TNFalpha transcripts and more highly acetylated histones at the TNFalpha locus compared to controls. Furthermore, patients with the highest levels of TNFalpha histone acetylation were more likely to have had consistently elevated erythrocyte sedimentation rates, and to have required cytotoxic use. Histone acetylation, associated with increased transcriptional competence of TNFalpha, may play a role in certain inflammatory aspects of the disease.

The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Publishing Authors By Initials

KE Sullivan,A Suriano,K Dietzmann,J Lin,D Goldman,MA Petri,KE Sullivan,A Suriano,K Dietzmann,J Lin,D Goldman,MA Petri,

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

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The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Clinical immunology (Orlando, Fla.)

VOLUME: 123

Page Numbers: 74-81

Journal Abbreviation: Clin. Immunol.

ISSN: 1521-6616

DAY: 5

MONTH: 02

YEAR: 2007

The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100883537

The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: immunology

Chemical & Substance for Abstract: The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus. Information

Substance Name: Tumor Necrosis Factor-alpha

Registry Number: 0

Grant and Affiliation Information for The TNFalpha locus is altered in monocytes from patients with systemic lupus erythematosus.

AFFILIATION: Allergy Immunology, The Children's Hospital of Philadelphia, 34th Street and Civic Ctr. Boulevard, Philadelphia, PA 19104, USA. sullivak@mail.med.upenn.edu

Country: United States

AGENCY: United States NIAID

GRANT: R01 AI051323

ACRONYM: AI

MEDLINETA: Clin Immunol

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