Chemokine production by rat alveolar macrophages is inhibited by taurine chloramine

Abstract

Taurine protects lung tissue from oxidant-induced damage in a variety of models that involve inflammation as a pathogenic feature. The mechanism of taurine protection is thought to be related to the formation and subsequent action of taurine chloramine (Tau-Cl). Tau-Cl results from the activity of a halide-dependent myeloperoxidase system associated with neutrophils. Since chemokines are secreted by activated alveolar macrophages and are prominently involved in propagating the inflammatory response in lung, we determined the effects of Tau-Cl on MCP-1 and MIP-2 production in NR8383, a cloned cell line derived from rat alveolar macrophages. Activation of NR8383 cells with LPS and IFN-gamma resulted in accumulation of MCP-1 and MIP-2 in the conditioned media over the following 24-h and this was inhibited by Tau-Cl in a concentration dependent fashion. Northern blot analyses of MCP-1 and MIP-2 mRNA expression revealed concentration dependent inhibition by Tau-Cl. Expression of MCP-1 transcripts was more potently inhibited by Tau-Cl relative to that of MIP-2. Since the promoter regions of these chemokine genes are regulated by NF-kappaB, nuclear protein extracts were evaluated for NF-kappaB binding to its sequence specific recognition site (EMSA). Tau-Cl treated cells expressed reduced nuclear NF-kappaB binding relative to the activated control cells. The composition of the NF-kappaB dimer contained predominately p50 and p65 subunits, but some c-Rel was also present. These results suggest that Tau-Cl inhibits production of chemokines by activated NR8383 cells through a mechanism that involves, in part, the NF-kappaB signaling pathway.