title: HMGB1 induced inflammatory effect is blocked by CRISPLD2 via MiR155 in hepatic fibrogenesis.
abstract: A number of studies have showed that High mobility group box-1 (HMGB1), which played key role in inflammation activation by triggering the toll like receptor 4 (TLR4) signaling axis in hepatic fibrogenesis, may share similar inflammation stimulating mechanism with LPS. Herein, we introduced a recently established anti-LPS protein cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) to investigate endogenous protection mechanism of HMGB1 induced inflammatory response. Our results shows that stromal cells and monocytes showed an evaluated pattern for CRISPLD2 expression after HMGB1 treatment, which was dependent on the integrity of TLR4 function. Pro-inflammatory Cytokines levels were significantly elevated after CRISPLD2 silencing despite the HMGB1 status. Soluble CRISPLD2 administration relieve the HMGB1 dependent pro-inflammatory cytokines release. Interestingly, we found that miRNA 155 play a key role in the process. Our data suggest that CRISPLD2 may have a unique anti-HMGB1 effect via miRNA and play an important role in immune balance.
authors.affiliation: Department of Infectious Disease, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
authors.forename: Haoye
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Pharmacy Department, The Third Xiangya Hospital of Central South University, Changsha 410013, China. Electronic address: liusk8618@163.com.
authors.forename: Shikun
authors.initials: S
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C525599:CRISPLD2 protein, human; D015815:Cell Adhesion Molecules; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D050835:Interferon Regulatory Factors; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D011993:Recombinant Fusion Proteins
keywords: HMGB1; Hepatic fibrogenesis; TLR4; micoRNA CRISPLD2