OBJECTIVE: Activation of pattern recognition receptors (PRR) may contribute to arthritis. Here, we elucidated the role of NOD2, a genetic cause of inflammatory arthritis, and several other PRR in a murine model of inflammatory arthritis. METHODS: The roles of CR3, TLR2, MyD88, NOD1, NOD2, Dectin-1 and Dectin-2 were tested in vivo in arthritis elicited by intra-articular injections of zymosan, the fungal cell wall components curdlan, laminarin and mannan, and the bacterial cell wall peptidoglycan. RESULTS: Dectin-1, and to a lesser extent Dectin-2, contributed to arthritis. TLR2, MyD88 and CR3 played non-essential roles. Observations based on injection of curdlan, laminarin or mannan supported the dominant role of the Dectin-1 pathway in the joint. We demonstrated differential roles for NOD1 and NOD2 and identified NOD2 as a novel and essential mediator of zymosan-induced arthritis. CONCLUSIONS: Together, Dectin-1 and NOD2 are critical, sentinel receptors in the arthritogenic effects of zymosan. Our data identify a novel role for NOD2 during inflammatory responses within joint.

innate immunity, zymosan, Arthritis models, NOD2, In vivo inflammation

• Compound ID: 4415
  

  -3)-b-D-Glcp-(1-

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  Structure type: homopolymer
  Trivial name: glucan, β-1,3-glucan, curdlan, curdlan-type polysaccharide 13140, paramylon, curdlan, laminarin, β-glucan, curdlan, β-(1,3)-glucan, β-(1,3)-glucan, curdlan, curdlan, β-1,3-glucan, paramylon, reserve polysaccharide, b-glucan, β-1,3-D-glucan, laminaran, botryosphaeran, laminaran type β-D-glucan, latiglucan I, pachymaran, Curdlan, zymosan A, β-glucan, curdlan, laminarin, zymosan, zymosan, glucan particles, zymosan, β-(1-3)-glucan, β-(1,3)-glucan, β-(1,3)glucan, pachymaran, D-glucan (DPn)540, pachyman, laminaran, curdlan, zymosan, zymosan, β-(1,3)-glucan, zymosan A, zymosan, β-1,3-glucan, curdlan, β-1,3-glucan, curdlan, β-1,3-glucan, curdlan, pachyman, β-(1,3)-glucan, curdlan, callose, a water-insoluble β-(1→3)-glucan, fermentum β-polysaccharide, water-insoluble glucan, alkali-soluble β-glucan (PeA3), alkali-soluble polysaccharide (PCAP), callose, laminarin
  Compound class: EPS, O-polysaccharide, cell wall polysaccharide, lipophosphoglycan, glycoprotein, LPG, glucan, polysaccharide, glycoside, β-glucan, β3-glucan, cell wall glucan
  Reference(s) to other database(s): GTC:G51056AN, GlycomeDB:157, CCSD:50049, CBank-STR:4225, CA-RN: 51052-65-4, GenDB:FJ3380871.1
  
   
  
  Saccharomyces cerevisiae
  CSDB ID 45573 (all data & tools)

An endophytic fungus Aspergillus terreus, var. boedijnii (Blochwitz) was isolated from red marine alga Laurencia ceylanica, J. Agardh, cultured in large scale and extracted with EtOAc. The above-mentioned extract yielded a new butyrolactone, 3-hydroxy-4-(4-hydroxyphenyl)-5-methoxycarbonyl-5-(4-hydroxy-3-formylbenzyl)-2,5-dihydro-2-furanone (1), along with the previously reported nine compounds, butyrolactone-1 (2), 6-hydroxymellin (3), (3R, 4R)-6,7-dimethoxy-4-hydroxymellin (4), (+)-territonin (5), (+)-territonin-A (6), (+)-asterrelenin (7), (+)-terrein (8), oleic acid (9) and glucopyranosyl-β-sitosterol (10), on column and preparative thin-layer chromatography. Compounds 1-8 were subjected to β-glucuronidase inhibitory activity test, and 1 showed a remarkable activity, while 2 and 7 showed moderate activity.

β-glucuronidase, Aspergillus terreus, Laurencia ceylanica, butyrolactone, 3-hydroxy-4-(4-hydroxyphenyl)-5-methoxycarbonyl-5-(4-hydroxy-3-formylbenzyl)-2, 5-dihydro-2-furanone

• Compound ID: 20490
  

  b-D-Glcp-(1-3)-Subst Subst = β-sitosterol = SMILES O{3}[C@H](C1)CC[C@@]2(C)C1=CC[C@]3([H])[C@@]2([H])CC[C@@]4(C)[C@]3([H])CC[C@]4([C@@H](C)CC[C@@H](CC)C(C)C)[H]

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  Structure type: monomer
  Trivial name: daucosterol, β-daucosterol, β-sitosterol, β-sitosterol-β-D-glucoside, androsine, saxifragifolin B, β-sitosterol 3-O-β-D-glucopyranoside
  Compound class: saponin glycoside, glycoside, steroid glycoside, triterpenoid glycoside
  Reference(s) to other database(s): GenDB:MK026953.1
  
   
  
  Aspergillus terreus var. boedijni
  CSDB ID 45044 (all data & tools)

HS002-II, a novel protein-bound polysaccharide with 44kDa molecular weight, was fractionated from submerged cultures of Hirsutella sinensis Liu, Guo, Yu & Zeng by DEAE-Sepharose and Sephacryl S200 chromatography. Based on the results of infrared spectroscopy, high performance liquid chromatography, methylation, amino acid analysis, NMR spectroscopy and atomic force microscopy, the polysaccharide moieties of HS002-II mainly contained a long backbone of (1→3)-linked α-d-ribofuranosyl units (1→4)-linked α-d-xylopyranosyl units and (1→4)-linked β-D-glucopyranosyl units, which was substituted at C-6. The two branches were β-D-mannopyranosyl residues and β-D-galactopyranosyl residues terminated with α-l-arabinopyranosyl residues, respectively. HS002-II consisted of 57.9% polysaccharide and 42.1% protein with the existence of N-type carbohydrate-protein linkage. In terms of the pro-inflammatory cytokines assay (NO, TNF-α, IL-1β and NF-κB) using murine macrophages cell line (RAW264.7), HS002-II exhibited significant immunomodulatory activity by stimulating the IκB-NF-κB pathway.

structure, cytokines, Immunostimulatory activity, Hirsutella sinensis Liu, Guo, Yu & Zeng, protein-bound polysaccharide

• Compound ID: 20491
  

  a-L-Arap-(1-6)-{{{-b-D-Manp-(1-6)-}}}/n=2/-b-D-Manp-(1-6)-+ | a-L-Arap-(1-6)-{{{-b-D-Galp-(1-6)-}}}/n=7/-b-D-Galp-(1-6)-+ | | | -4)-a-D-Xylp-(1-4)-b-D-Glcp-(1-4)-{{{-b-D-Glcp-(1-4)-}}}/n=29/-b-D-Glcp-(1-3)-a-D-Ribf-(1-

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  Structure type: structural motif or average structure ; 44000
  Compound class: polysaccharide
  
   
  
  Hirsutella sinensis
  CSDB ID 45045 (all data & tools)