A proposed scheme for regulation of TNFα induction in the LPS-stimulated human PMN. (Left) In the resting cell, RhoA suppresses NF-κB activation and TNFα expression. This may occur through its inhibition of Cdc42 and possibly also through a Cdc42-independent mechanism. RhoA activity in the resting PMN is p38- and Cdc42-independent. (Right) In the LPS-stimulated PMN, we have previously reported that p38 is activated⁸ and promotes the activation of NF-κB⁸ and Cdc42.³⁰  LPS-activated Cdc42 regulates RhoA activation. Downstream of RhoA, ROCKα is activated and promotes TNFα protein expression. LPS-activated p38 and Cdc42 may regulate TNFα protein through ROCKα, but ROCKα-independent pathways are also possible (not shown).