Novel transglutaminase inhibitors reverse the inflammation of allergic conjunctivitis

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

Research output: Contribution to journalArticle

102 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalJournal of Clinical Investigation
Volume111
Issue number1
DOIs
Publication statusPublished - 2003 Jan

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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