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Novel transglutaminase inhibitors reverse the inflammation of allergic conjunctivitis
Joonhong Sohn, … , Joo-Yong Kim, Soo-Youl Kim
Joonhong Sohn, … , Joo-Yong Kim, Soo-Youl Kim
Published January 1, 2003
Citation Information: J Clin Invest. 2003;111(1):121-128. https://doi.org/10.1172/JCI15937.
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Novel transglutaminase inhibitors reverse the inflammation of allergic conjunctivitis

Abstract

Steroidal anti-inflammatory drugs induce proteins that inhibit phospholipase A2 (PLA2), including uteroglobin and lipocortin-1 (annexin I). Uteroglobin and lipocortin-1 retain several conserved sequences. Based on these sequences, several nonapeptides (antiflammins) were synthesized. These nonapeptides were shown to have anti-inflammatory effects in vitro and in vivo, possibly by inhibiting PLA2. Subsequent research showed that PLA2 is activated by transglutaminase 2 (TGase 2). We hypothesize here that TGase 2 inhibitors may increase the anti-inflammatory efficacy of inhibiting PLA2 activity. To test this theory, we constructed recombinant peptides containing sequences from pro-elafin (for inhibition of TGase 2), and from lipocortin-1, lipocortin-5, and uteroglobin (for inhibition of PLA2). The recombinant peptides, which had dual inhibitory effects on purified TGase 2 and PLA2, reversed the inflammation of allergic conjunctivitis to ragweed in a guinea pig model. The present work suggests that novel recombinant peptides may be safe and effective agents for the treatment of various inflammatory diseases.

Authors

Joonhong Sohn, Tae-Im Kim, Young-Hee Yoon, Joo-Yong Kim, Soo-Youl Kim

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