INTERLEUKIN-2 PRODUCTION IN SJOGREN'S SYNDROME

  • Dang, Howard (PI)
  • Talal, Norman (PI)

Project: Research project

Project Details

Description

Primary Sjogren's syndrome (SS) is a chronic autoimmune disease
characterized by 1) serum autoantibodies, 2) increased numbers of CD5+ B
cells, 3) lymphocytic infiltration of salivary, lacrimal and other exocrine
glands with a tendency to generalized lymphoproliferation that can
terminate as a malignant lymphoma. The long-term objective of this
application is to acquire knowledge leading to 1) a better understanding of
the mechanisms responsible for the immune dysregulation in SS, and 2)
possible development of new therapeutic modalities (such as polyamine
inhibitors) for this disease. Peripheral blood mononuclear cells (PBMNC)
from SS patients produce decreased amounts of interleukin-2 (IL-2)
following stimulation with PHA or anti-CD3. There is also a transmembrane
signalling defect in SS T cells revealed by exposure to PMA and ionomycin.
Since oxidation products of polyamines diminish IL-2 production by normal
and rheumatoid arthritis (RA) T cells, a similar mechanism may be operating
and primary SS. The specific aims and methodologies are the following: 1. Measure polyamine levels (by HPLC), IL2 production (by bioassay) and
the effect of polyamine inhibitors (like DEMO) on IL2 production in SS
PBMNC. 2. Measure IL2 mRNA levels in SS PBMNC (by slot and Northern blots) and
identify possible pre- or post-transcriptional defects (hydrolysis of
phosphoinositides by ion exchange chromatography, rise in intracellular
calcium by Indo-1 and FACS analysis, diacylglycerol-dependent activation,
IL2 protein biosynthesis and secretion by ELISA). 3. Attempt to correct a possible defect in SS by polyamine inhibitors, or
create a defect in normal PBMNC using polyamines plus polyamine oxidase.
StatusFinished
Effective start/end date7/1/908/31/96

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)
  • Dentistry(all)

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