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Hyaluronic acid fragments evoke Kupffer cells via TLR4 signaling pathway

  • In Memoriam: Professor Ray Wu
  • Published:
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Abstract

Kupffer cells, expressing toll-like receptor 4 (TLR4), play a central role in hepatic ischemia/reperfusion (I/R) injury. Hyaluronic acid (HA) fragments, degradative products of high-molecular-weight HA (HMW-HA), acquire the ability to activate immune cells under inflammatory conditions. Here we investigated whether HA fragments could activate Kupffer cells and analyzed the underlying mechanism. Kupffer cells were isolated from wild-type mice (WT, C3H/HeN) and TLR4 mutant mice (C3H/HeJ) and HA fragments were produced by the methods of enzyme digestion and chromatography. Then Kupffer cells were stimulated by HA fragments or other control stimuli. The activation of Kupffer cells was estimated as the release of pro-inflammatory cytokines. The activation of p38 MAPK pathway of Kupffer cells was checked and blocking experiments were done as well. The results indicated that HA fragments acquired the ability to activate Kupffer cells in vitro, which was TLR4 dependent and not due to contamination of lipopolysaccharide. Experiments of p38 MAPK kinase inhibition by SB-203580 verified p38 MAPK was required in HA fragments induced Kupffer cells activation. This suggests that HA fragments, degradative products of one of the major glycosaminoglycans of the extracellular matrix, play critical roles in Kupffer cell activation mediated by TLR4 signaling pathway, which is, at least partially, dependent on p38 MAPK activation.

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Authors and Affiliations

  1. Department of Emergency Surgery, Union Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, 430022, China

    JinXiang Zhang & ChunFang Jiang

  2. Department of Medical Genetics, Tongji Medical College Affiliated to Huazhong University of Science and Technology, Wuhan, 430030, China

    Hui Wang

  3. Department of Ophthalmology, Union Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, 430022, China

    Qing Xiao

  4. Department of Medical Immunology, Tongji Medical College Affiliated to Huazhong University of Science and Technology, Wuhan, 430030, China

    HuiFang Liang & ZhuoYa Li

  5. Department of General Surgery, Union Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, 430022, China

    HeShui Wu & QiChang Zheng

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  1. JinXiang Zhang
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Correspondence to JinXiang Zhang.

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These anthors contributed equally to this work

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Zhang, J., Wang, H., Xiao, Q. et al. Hyaluronic acid fragments evoke Kupffer cells via TLR4 signaling pathway. SCI CHINA SER C 52, 147–154 (2009). https://doi.org/10.1007/s11427-009-0002-y

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  • DOI: https://doi.org/10.1007/s11427-009-0002-y

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