Proposed low-dose doxycycline to suppress micro- and nanoplastic-induced inflammation

MNP exposure (inhalation/ingestion) increases ROS, which amplifies NF-κB/MAPK signaling, primes and activates the NLRP3-caspase-1 inflammasome, and dysregulates MMP-2/9, culminating in tissue inflammation across organs.

Tetracyclines directly inhibit NF-κB/MAPK and NLRP3-caspase-1 and reduce MMP-2/9 activity (via Zn²⁺ chelation), with secondary, context-dependent reductions in ROS.

Notation: ⊕ activation; ⊖ inhibition. Solid line = direct suppression (e.g., Zn²⁺ chelation, pathway inhibition). Dashed line = indirect suppression via upstream effects. Capsule icons denote tetracyclines. Organ icons illustrate principal target systems.