Mast Cell-Mediated Inhibition of Abdominal Neutrophil Inflammation by a PEGylated TLR7 Ligand

作者：Hayashi Tomoko^*; Yao Shiyin; Crain Brian; Chan Michael; Cottam Howard B; Lao Fitzgerald; Carson Dennis A; Corr Maripat

来源：Mediators of Inflammation, 2012, 2012: 262394.

DOI：10.1155/2012/262394

Although the mechanisms for sustained chemokine gradients and recurring cell infiltration in sterile peritonitis have not been elucidated, toll-like receptors (TLRs) have been implicated. To abate the deleterious recruitment of neutrophils in sterile inflammation, we repeatedly administered a TLR7 ligand that hyposensitized to TLR7 and receptors that converged on the MyD88-signaling intermediary and reduced cellular infiltration in murine autoimmune models of multiple sclerosis and arthritis. To reduce potential adverse effects, a polyethylene glycol polymer was covalently attached to the parent compound (Tolerimod1). The proinflammatory potency of Tolerimod1 was 10-fold less than the unconjugated TLR7 ligand, and Tolerimod1 reduced neutrophil recruitment in chemically induced peritonitis and colitis. The effects of Tolerimod1 were mediated by the radioresistant cells in radiation chimeric mice and bymast cells in reconstitutedmast cell-deficient mice (Kit(W-sh)). Although the Tolerimod1 had weak proinflammatory agonist activity, it effectively reduced neutrophil recruitment in sterile peritoneal inflammation.

• 出版日期2012