title: Mesencephalic astrocyte-derived neurotrophic factor is involved in inflammation by negatively regulating the NF-κB pathway.
abstract: Inflammation can cause endoplasmic reticulum (ER) stress and therefore activates the unfolded protein response (UPR). ER stress and the consequent UPR have the potential to activate NF-κB. However, the factors mediating the crosstalk between ER stress and the NF-κB pathway remain unclear. Here, we determined that ER stress inducible protein Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) was up-regulated in autoimmune diseases and inflammatory disease models. Inflammation caused MANF to relocalize to the nuclei. MANF interacted with the DNA binding domain of p65 through its C-terminal SAP-like domain in the nuclei under the condition of inflammation or ER stress. MANF consequently inhibited p65-mediated transcriptional activation by interfering with the binding of p65 to its target genes promoters. Consistently, MANF suppressed the expressions of NF-κB-dependent target genes and the proliferation of inflammatory synoviocytes. These findings suggest that MANF may be a negative regulator of inflammation and mediate the crosstalk between the NF-κB pathway and ER stress.
authors: 1] School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China [3] Department of Anesthesiology of the First Affiliated Hospital, Anhui Medical University, Hefei 230022, Anhui, China.
authors: Lijian
authors: L
authors: Chen
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Lijie
authors: L
authors: Feng
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Xia
authors: X
authors: Wang
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Jian
authors: J
authors: Du
authors: Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Ying
authors: Y
authors: Chen
authors: 1] School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Wen
authors: W
authors: Yang
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Chengyue
authors: C
authors: Zhou
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Li
authors: L
authors: Cheng
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Yujun
authors: Y
authors: Shen
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China [3] Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201, USA.
authors: Shengyun
authors: S
authors: Fang
authors: School of Pharmacy, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Jun
authors: J
authors: Li
authors: 1] School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China [2] Institute of Biopharmaceuticals, Anhui Medical University, Hefei 230032, Anhui, China.
authors: Yuxian
authors: Y
authors: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha
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