Dimerized
translationally controlled tumor protein (dTCTP) amplifies allergic responses through activation of several types of immune cells and release of inflammatory mediators. In particular, dTCTP plays an important role in histamine release by triggering mast cells and has been proposed as a target in the treatment of allergic diseases. dTCTP-binding
peptide 2 (
dTBP2) is known to attenuate severe
allergic rhinitis and
asthma through inhibition of dTCTP activity on airway epithelial cells and T cells; however, it is unclear whether
dTBP2 affects mast cell function and
mast cell disease. In this study, we explored the effects of
dTBP2 on mast cell degranulation and
allergen-induced
anaphylactic reactions. We found that bacterial product
lipopolysaccharide increased the expression of dTCTP in mast cells and rapidly released dTCTP by the mast cell stimulator
compound 48/80. Interestingly, the released dTCTP further promoted mast cell degranulation in an autocrine activation manner and increased
calcium mobilization in mast cells, which is essential for degranulation. Furthermore,
dTBP2 directly and dose-dependently inhibited in vitro mast cell degranulation enhanced by
compound 48/80, suggesting a direct and potent anti-anaphylactic activity of
dTBP2.
dTBP2 also significantly suppressed the dTCTP-induced degranulation and histamine release through inhibition of the
p38 MAPK signaling pathway and suppression of lysosomal expansion and
calcium mobilization in mast cells. More importantly, in vivo administration of
dTBP2 decreased mortality and significantly attenuated histamine release and inflammatory
cytokine production in
compound 48/80-induced systemic
anaphylactic reactions. These results suggest that
dTBP2 is beneficial for the control of
anaphylaxis with increased dTCTP.