Interleukin-12 synthesis is a required step in trehalose dimycolate-induced activation of mouse peritoneal macrophages.

摘要: Trehalose dimycolate (TDM), a glycolipid present in the cell wall of Mycobacterium spp., is powerful immunostimulant. TDM primes murine macrophages (Mphi) to produce nitric oxide (NO) and develop antitumoral activity upon activation with low doses lipopolysaccharide (LPS). In this study, we investigated ability induce interleukin 12 (IL-12) role cytokine TDM-induced Mphi. RNA isolated from peritoneal exudate cells (PEC) collected at different times after injection was used determine IL-12 (p35 p40 subunits) gamma interferon (IFN-gamma) mRNA levels by semiquantitative reverse transcriptase-PCR. Constitutive expression IL-12p35 observed PEC untreated as well TDM-injected mice. contrast, IL-12p40 subunit almost undetectable control but dramatically upregulated peaked 8 h subsided baseline 39 postinjection. also able IFN-gamma expression; however, kinetics induction that IL-12p40. Maximal were reached 24 did not return 4 days. addition, pretreatment mice neutralizing monoclonal antibodies directed against (C15.6.7 C15.1.2) blocked TDM-treated We further determined if and/or contributes vivo priming effect on treated anti-IL-12 or anti-IFN-gamma (XMG.1.6) antibodies. TDM-primed Mphi then activated vitro LPS tested for their NO cytostatic toward cocultivated L1210 tumor cells. Priming completely neutralization either demonstrated an absence tumoricidal production TDM-elicited presence LPS. Taken together our results show TDM, defined molecule M. tuberculosis, induces IL-12. Moreover, synthesis mediates mouse through induction.