TY - JOUR
TI - A link between interferon and augmented plasmin generation in exocrine
gland damage in Sjogren's syndrome
AU - Gliozzi, Maria
AU - Greenwell-Wild, Teresa
AU - Jin, Wenwen and
AU - Moutsopoulos, Niki M.
AU - Kapsogeorgou, Efstathia
AU - Moutsopoulos,
AU - Haralampos M.
AU - Wahl, Sharon M.
JO - Journal of Autoimmune Diseases
PY - 2013
VL - 40
TODO - null
SP - 122-133
PB - ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
SN - 1740-2557
TODO - 10.1016/j.jaut.2012.09.003
TODO - tPA; Macrophage; Salivary gland; Cytokine; Plasminogen; MMP
TODO - Sjogren’s syndrome is an autoimmune disease that targets exocrine
glands, but often exhibits systemic manifestations. Infiltration of the
salivary and lacrimal glands by lymphoid and myeloid cells orchestrates
a perpetuating immune response leading to exocrine gland damage and
dysfunction. Th1 and Th17 lymphocyte populations and their products
recruit additional lymphocytes, including B cells, but also large
numbers of macrophages, which accumulate with disease progression. In
addition to cytokines, chemokines, chitinases, and lipid mediators,
macrophages contribute to a proteolytic milieu, underlying tissue
destruction,, inappropriate repair, and compromised glandular functions.
Among the proteases enhanced in this local, environment are matrix
metalloproteases (MMP) and plasmin, generated by plasminogen activation,
dependent upon plasminogen activators, such as tissue plasminogen
activator (tPA). Not previously associated with salivary gland
pathology, our evidence implicates enhanced tPA in the context of
inflamed salivary glands revolving around lymphocyte-mediated activation
of macrophages. Tracking down the mechanism of macrophage plasmin
activation, the cytokines IFN gamma and to a lesser extent, IFN alpha,
via Janus kinase (JAK) and signal transducer and activator of
transcription (STAT) activation, were found to be pivotal for driving
the plasmin cascade of proteolytic events culminating in perpetuation of
the inflammation and tissue damage, and suggesting intervention
strategies to blunt irreversible tissue destruction. Published by
Elsevier Ltd.
ER -