Enzyme degradation and proinflammatory activity in arthritogenic and nonarthritogenic Eubacterium aerofaciens cell walls.
Two almost-identical strains of Eubacterium aerofaciens isolated from the normal human gut flora were used. The cell wall (CW) of one strain with a peptidoglycan (PG) type A4alpha induces chronic arthritis in the rat after a single intraperitoneal injection, whereas CW of the other with PG type A4beta induces only a transient acute arthritis. The CW of the arthritogenic E. aerofaciens was a twofold-more-potent stimulator of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP-1) than the nonarthritogenic CW. After degradation with mutanolysin, the capacity of the arthritogenic PG to stimulate production of TNF-alpha and MCP-1 was significantly increased, whereas that of the nonarthritogenic PG was significantly decreased. In other words, after enzyme degradation the arthritogenic PG had a four- to fivefold-stronger stimulatory capacity than that of the enzyme-treated nonarthritogenic PG. These findings indicate that the arthritogenicity of CW or a PG is not dependent on the enzyme resistance alone but also on how the PG fragments released by enzyme degradation stimulate the production of proinflammatory cytokines.
Zhang
X
X
Department of Medical Microbiology, Turku Immunology Center, University of Turku, Turku, Finland. xzhang@utu.fi
Rimpiläinen
M
M
Simelyte
E
E
Toivanen
P
P
D000818:Animals; D001170:Arthritis, Infectious / Q000209:etiology*; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D002240:Carbohydrate Sequence; D002473:Cell Wall / Q000276:immunology* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004064:Digestive System / Q000382:microbiology; D010450:Endopeptidases / Q000378:metabolism; D005051:Eubacterium / Q000145:classification / Q000472:pathogenicity*; D016908:Gram-Positive Bacterial Infections / Q000150:complications*; D008099:Liver / Q000737:chemistry; D017737:Macrophages, Peritoneal / Q000276:immunology; D008969:Molecular Sequence Data; D009112:Muramic Acids / Q000032:analysis; D009113:Muramidase / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013154:Spleen / Q000737:chemistry; D013583:Synovial Membrane / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018932:Chemokine CCL2; D009112:Muramic Acids; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha; D009113:Muramidase; D010450:Endopeptidases; C021816:mutanolysin