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Although the physiological role of MF6p\/HDMs in trematode parasites is not fully understood, their potential biological function in maintaining heme homeostasis and modulating host immune response has been proposed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A gene encoding the MF6p\/HDM of<jats:italic>Clonorchis sinensis<\/jats:italic>(CsMF6p\/HDM) was cloned. Recombinant CsMF6p\/HDM (rCsMF6p\/HDM) was expressed in<jats:italic>Escherichia coli<\/jats:italic>. The biochemical and immunological properties of rCsMF6\/HDM were analyzed. CsMF6p\/HDM induced pro-inflammatory response in RAW 264.7 cells was analyzed by cytokine array assay, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay. The structural feature of CsMF6p\/HDM was analyzed by three-dimensional modeling and molecular docking simulations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CsMF6p\/HDM shares a high level of amino acid sequence similarity with orthologs from other trematodes and is expressed in diverse developmental stages of the parasite. The rCsMF6p\/HDM bound to bacteria-derived lipopolysaccharide (LPS), without effectively neutralizing LPS-induced inflammatory response in RAW 264.7 macrophage cells. Rather, the rCsMF6p\/HDM induced pro-inflammatory immune response, which is characterized by the expression of TNF-\u03b1 and IL-6, in RAW 264.7 cells. The rCsMF6p\/HDM-induced pro-inflammatory immune response was regulated by JNK and p38 MAPKs, and was effectively down-regulated<jats:italic>via<\/jats:italic>inhibition of NF-\u03baB. The structural analysis of CsMF6p\/HDM and the docking simulation with LPS suggested insufficient capture of LPS by CsMF6p\/HDM, which suggested that rCsMF6p\/HDM could not effectively neutralize LPS-induced inflammatory response in RAW 264.7 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although rCsMF6p\/HDM binds to LPS, the binding affinity may not be sufficient to maintain a stable complex of rCsMF6p\/HDM and LPS. Moreover, the rCsMF6p\/HDM-induced pro-inflammatory response is characterized by the release of IL-6 and TNF-\u03b1 in RAW 264.7 macrophage cells. The pro-inflammatory response induced by rCsMF6p\/HDM is mediated<jats:italic>via<\/jats:italic>NF-\u03baB-dependent MAPK signaling pathway. These results collectively suggest that CsMF6p\/HDM mediates<jats:italic>C. sinensis<\/jats:italic>-induced inflammation cascades that eventually lead to hepatobiliary diseases.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13071-020-3882-0","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T14:02:49Z","timestamp":1578924169000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Clonorchis sinensis MF6p\/HDM (CsMF6p\/HDM) induces pro-inflammatory immune response in RAW 264.7 macrophage cells via NF-\u03baB-dependent MAPK pathways"],"prefix":"10.1186","volume":"13","author":[{"given":"Jung-Mi","family":"Kang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Gi","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u01b0\u01a1ng Giang","family":"L\u00ea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woon-Mok","family":"Sohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byoung-Kuk","family":"Na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"3882_CR1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1079\/JOH2005300","volume":"79","author":"HJ Rim","year":"2005","unstructured":"Rim HJ. 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