Enzyme degradation and proinflammatory activity in arthritogenic and nonarthritogenic Eubacterium aerofaciens cell walls

Two almost-identical strains of Eubacterium aerofaciens isolated from the n ormal human gut flora were used. The cell wall (CW) of one strain with a pe ptidoglycan (PG) type A4 alpha induces chronic arthritis in the rat after a single intraperitoneal injection, whereas CW of the other with PG type A4 beta 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 chemoattract ant protein 1 (MCP-1) than the nonarthritogenic CW. After degradation with mutanolysin, the capacity of the arthritogenic PG to stimulate production o f TNF-alpha and MCP-1 was significantly increased, whereas that of the nona rthritogenic PG was significantly decreased. In other words, after enzyme d egradation the arthritogenic PG had a four- to fivefold-stronger stimulator y capacity than that of the enzyme-treated nonarthritogenic PG. These findi ngs indicate that the arthritogenicity of CW or a PG is not dependent on th e enzyme resistance alone but also on how the PG fragments released by enzy me degradation stimulate the production of proinflammatory cytokines.