Sodium azide suppresses LPS-induced expression MCP-1 through regulating IκBζ and STAT1 activities in macrophages

Sodium azide (NaN₃) is a chemical compound with multiple toxic effects on vascular and neuronal systems, causing hypotension and neurotoxicity, respectively. In order to test its effects on the immune system, human and mouse macrophage-like cell lines were treated with nontoxic doses of NaN₃ and the changes in LPS-induced inflammatory activation was measured. Interestingly, the LPS-induced expression of monocyte chemoattractant protein (MCP)-1 was suppressed by NaN₃ without affecting the expression of IL-8 and TNF-α. Further analysis of cellular signaling mediators involved in the expression of these cytokines revealed that NaN₃ suppressed the LPS-induced activation of signal transducers and activator of transcription (STAT)1 and inhibitor of κB (IκB) ς, which are involved in the LPS-induced expression of MCP-1, while the LPS-induced activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) was not affected. The LPS-induced expression of MCP-2 and CXCL10, which are also regulated by STAT1, was suppressed by NaN₃. Similarly, the LPS-induced expression of IL-6, which is regulated by IκBζ, was suppressed by NaN₃. These results demonstrate that NaN₃ selectively suppresses the LPS-induced expression of pro-inflammatory mediators through the suppression of STAT1 and IκBζ activation. These new findings about the activity of NaN₃ may contribute to the development of specific regulators of macrophage activity during acute and chronic inflammation.