First evidence of the activation of Cg-timp, an immune response component of Pacific oysters, through a damage-associated molecular pattern pathway

In a previous work, we characterized a Crassostrea gigas cDNA (Cg-timp) encoding a protein which presents all the features of vertebrate tissue inhibitor of metalloproteinase (TIMP). The expression pattern of this gene led us to propose that Cg-timp is an important factor in oyster wound healing and defense mechanisms. Here we describe the analysis of Cg-timp expression in oysters challenged by live or dead bacteria as well as by bacterial secretory/excretory products and metalloproteinase. Surprisingly, bacterial secretory/excretory products activate Cg-timp gene expression whereas heat-inactivated ones do not. To address the question of the signal transduction pathway involved in Cg-timp gene activation, we isolated and sequenced Cg-timp promoter and upstream region. A 1-kb genomic DNA fragment flanking the 5'-end of the gene contains several regulatory elements and notably three NF-kappaB binding sites. The potential involvement of these motifs in Cg-timp gene regulation is discussed.