Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois 60153, USA
Uteroglobin/Clara cell 10-kDa protein (UG/CC10) is a hormonally
regulated small secretory protein that has a variety of
in vitro and
in vivo pharmacological effects. These include a potent
anti-inflammatory activity and inhibitory effects on neutrophil
migration, thrombin-induced platelet aggregation,
in vitro chemoinvasion,
as well as "tumor suppressor"-like effects and other properties.
Several mechanisms of action have been proposed for these effects.
Pharmacological properties suggest that UG itself or substances
derived from it may be used as experimental drugs for several
indications. The group of oligopeptides collectively known as
"antiflammins" (AFs) were originally described in 1988. Their
design was derived from the region of highest sequence similarity
between UG and another group of proteins with anti- inflammatory
properties, the lipocortins or annexins. Nanomolar concentrations
of these peptides can reproduce several of the pharmacological
activities of UG, including its
in vivo anti-inflammatory effects
and inhibition of platelet aggregation. The AFs have been safely
and effectively used to suppress inflammation and fibrosis in
several animal models. Progress in clarifying the mechanism
of action of the AFs may facilitate the structure-based design
of a novel class of potent anti-inflammatory, antichemotactic
drugs.
