Figure 5: MiR-146a is a negative regulator of the NF-κB signaling pathway. MiR-146a targets TNF receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1), two upstream adaptor proteins on the nuclear factor-kappaB (NF-κB) pathway thus inhibiting synthesis of pro-inflammatory cytokines. Interestingly, NF-κB induces miR-146a transcription to control the miR-146a levels in the cells. This feedback mechanism may contribute to maintaining a delicate equilibrium of pro-inflammatory and anti-inflammatory states in normal physiological conditions, which is often disrupted in pathological conditions and under cellular stresses such as following TBI. Thus, manipulation of miR-146a levels may have therapeutic benefits in intervening undesirable inflammatory responses related to cellular stressors. DAMPs: Damage-associated molecular pattern molecules; IKK: IkappaB kinase; IκB: IkappaB; IL-1R: interleukin-1 receptor; MYD88: myeloid differentiation primary response 88; PAMPs: pathogen-associated molecular pattern molecules; TLR: Toll-like receptor.