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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

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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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Figure 2

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The effects of various peptides on activation of PLA2 by TGase 2. (a) Pu...
The effects of various peptides on activation of PLA2 by TGase 2. (a) Purified PLA2 was preincubated with different amounts of TGase 2 for 15 minutes before assay. PLA2 activity was increased by incubation with TGase 2 in a dose-dependent manner. Data are presented as mean ± SD from three repeats of each TGase 2 concentration. (b) Purified PLA2 was preincubated with the peptides and 1 × 10–3 U TGase 2 for 15 minutes before assay. The recombinant peptide R2 markedly decreased PLA2 activity, although most AFs (A1–A3) and E3 inhibited PLA2 activity. Data are presented as mean ± SD from three separate experiments.

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