Inhibition of MCP-1 and MIP-2 transcription and translation by mimosine in muscle tissue infected with the parasite Trichinella spiralis.

Abstract

Mimosine is a non-toxic plant aminoacid which is an effective inhibitor of DNA replication by acting at the S-phase. In this study we infected mice with T. spiralis, a nematode parasite, and studied the inflammatory response through the determination of MIP-2, a C-X-C chemokine and MCP-1, a C-C chemokine in the inflamed area around the parasitic cyst. The animals were infected and their diaphragms were tested for inflammatory response. MCP-1 and MIP-2 was tested after 1, 10, 20, 30, and 40 days post inoculation, before and after mimosine treatment. The inflammatory index was calculated by counting the white blood cells around the nematode cysts, while expression of MIP-2 and MCP-1 was calculated by ELISA method and transcription by Northern blot and RT-PCR. Here we found that mimosine strongly inhibited the inflammatory index in the diaphragmatic tissue at 10, 20, 30 and 40 days post-treatment. In these experiments, mimosine had no effect on the number of cysts produced. In addition, we found that MCP-1 transcription and translation was completely inhibited by mimosine, while MIP-2 transcription and translation was partially inhibited at 30 and 40 days; yet it was totally inhibited after 10 and 20 days in encysted diaphragm tissue infected by T. spiralis. Our studies suggest that mimosine has an inhibitory effect through the inhibition of cytoplasmatic serine hydroxymethyltransferase altering the cell cycle of white blood cells. This study suggests for the first time the premise that mimosine acts as an anti-inflammatory compound.