Novel transglutaminase inhibitors reverse the inflammation of allergic conjunctivitis

Abstract

2 ), 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 PLA 2 . Subsequent research showed that PLA 2 is activated by transglutaminase 2 (TGase 2). We hypothesize here that TGase 2 inhibitors may increase the anti-inflammatory efficacy of inhibiting PLA 2 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 PLA 2 ). The recombinant peptides, which had dual inhibitory effects on purified TGase 2 and PLA 2 , 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.

Gene profiling reveals decreased expression of uteroglobin and other anti‐inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis

“…Peptides derived from uteroglobin are among the most potent anti-inflammatory agents identified to date [16]. Recently, a peptide of this kind was successfully tested in an animal model of allergic conjunctivitis [17]. The relevance of these anti-inflammatory effects is supported by decreased local expression of uteroglobin protein in asthma [18].…”

Tranglutaminase 2 contributes to the asthmatic inflammation by modulating activation of alveolar macrophages

“…Several studies have shown that TG2 is abundantly expressed in endothelial cells, macrophages, and smooth muscle cells, 9 and that it is involved in several inflammatory diseases, such as celiac disease, arthritis, and lupus 10 . Once activated by tissue injury, TG2 induces inflammatory and fibrogenic responses 11‐15 . Although the expression of TG2 is upregulated by Th2 cytokines in M2 macrophages, 16 little is known about the role of TG2 in macrophage activation in asthmatic airways.…”

The Outside-In Journey of Tissue Transglutaminase in Cancer

“…Indirect evidence of TG2 involvement in inflammation was provided by several studies using inflammatory disease models. Two reports have shown decreased inflammation in animal models of allergic conjunctivitis [ 124 ] and lipopolysaccharide (LPS)-induced lung inflammation [ 125 ], upon treatment with octapeptide R2 (KVLDGQDP) targeting TGase activity. In allergic asthma models, TG2 induced the expression of numerous signaling molecules associated with airway inflammation and remodeling [ 126 ].…”