The molecular mechanism of
transglutaminase II (TGaseII)-mediated allergic
inflammation remains largely unknown. TGaseII, induced by
antigen stimulation, showed an interaction and co-localization with FcϵRI. TGaseII was necessary for in vivo allergic
inflammation, such as triphasic cutaneous reaction, passive cutaneous anaphylaxis, and passive systemic
anaphylaxis. TGaseII was necessary for the enhanced metastatic potential of B16F1
melanoma cells by passive systemic
anaphylaxis. TGaseII was shown to be a secreted
protein. Recombinant TGaseII
protein increased the histamine release and β-
hexosaminidase activity, and enhanced the metastatic potential of B16F1 mouse
melanoma cells. Recombinant TGaseII
protein induced the activation of
EGF receptor and an interaction between
EGF receptor and FcϵRI. Recombinant TGaseII
protein displayed angiogenic potential accompanied by allergic
inflammation. R2
peptide, an inhibitor of TGaseII, exerted negative effects on in vitro and in vivo allergic
inflammation by regulating the expression of TGaseII and FcϵRI signaling.
MicroRNA (miR)-218 and miR-181a, decreased during allergic
inflammation, were predicted as negative regulators of TGaseII by
microRNA array and TargetScan analysis. miR-218 and miR-181a formed a negative feedback loop with TGaseII and regulated the in vitro and in vivo allergic
inflammation. TGaseII was necessary for the interaction between mast cells and macrophages during allergic
inflammation. Mast cells and macrophages, activated during allergic
inflammation, were responsible for the enhanced metastatic potential of
tumor cells that are accompanied by allergic
inflammation. In conclusion, the TGaseII/miR-218/-181a feedback loop can be employed for the development of anti-
allergy therapeutics.