Minocycline reverses IL-17A/TRAF3IP2-mediated p38 MAPK/NF-κB/iNOS/NO-dependent cardiomyocyte contractile depression and death

Minocycline, an FDA-approved second-generation semisynthetic tetracycline, exerts antioxidant, anti-apoptotic and anti-inflammatory effects, independent of its antimicrobial properties. Interleukin (IL)-17A is an immune and inflammatory mediator, and its sustained induction is associated with various cardiovascular diseases. Here we investigated (i) whether IL-17A induces cardiomyocyte contractile depression and death, (ii) whether minocycline reverses IL-17A's negative inotropic effects and (iii) investigated the underlying molecular mechanisms. Indeed, treatment with recombinant mouse IL-17A impaired adult cardiomyocyte contractility as evidenced by a 34% inhibition in maximal velocity of shortening and relengthening after 4 h (P