Characterization of a novel protein identified by proteomics analysis as a modulator of inflammatory networks in...

Inflammatory response is an innate host defense mechanism, and its regulation is essential for the host to get rid of harm by the excessive reactions. We first utilized proteomics approach to identify amphioxus humoral fluid proteins in response to LPS-induced inflammation. A total of 26 differentially expressed proteins, mainly involved in energy metabolism and cytoskeleton rearrangement processes, were identified between LPS-treated and control animals. Furthermore, we found a single uncharacterized protein (termed BjIM1) out of the most up-regulated ones, and examined its role in the regulation of immune and inflammatory responses. BjIM1 is predominantly expressed in the hepatic caecum, and its promoter sequence includes many binding sites for immune-relevant transcription factors. Importantly, recombinant BjIM1 (rBjIM1) is able to inhibit LPS-induced up-regulation of TLR pathway genes, such as MyD88, IKK, NF-κB1, Rel, p38, JNK and AP-1, indicating that BjIM1 may negatively regulate the TLR signaling pathway in amphioxus. Moreover, rBjIM1 also modulates the expression of genes involved in the interaction network of inflammation, energy metabolism and cytoskeleton rearrangement, including SIRT1, Rac1 and NOX2, in the LPS-induced inflammatory response in amphioxus. Collectively, our studies suggest that BjIM1 is an uncharacterized protein functioning as a modulator of inflammatory networks in amphioxus.