Toll-like receptor (TLR) signaling: stimulation of TLRs by periodontal pathogen associated molecular patterns triggers the association of myleloid differentiation primary-response protein 88 (MyD88), which in turn recruits IL-1 receptor associated kinase-4 (IRAK) [which phosphorylates IRAK1 (represented by IRAK)]. Tumor-necrosis factor receptor associated factor-6 (TRAF6) is also recruited to the phosphorylated IRAK complex. IRAK/TRAF6 then dissociate from the receptor complex to a new complex with transforming growth factor β-activated kinase (TAK1) along with TAK-1 and -2 binding protein (TAB1 and -2) (data not shown) which phosphorylate TAK1. TAK1, in turn, phosphorylates both mitogen activated protein kinase kinases-3 and -6 (MKK3, MKK6) and the inhibitor of nuclear factor κB (IκB)-kinase complex (IKK complex) (data not shown). The IKK complex then phosphorylates IκB, which allows nuclear factor-kappa B (NF-κB) transcription factors (p50/p65) to translocate to the nucleus and induce gene expression of cytokine genes. Similarly, MKK3/6 can phosphorylate p38 mitogen-activated protein kinase (MAPK) to activate activator protein-1 transcription factors and initiate gene expression. In addition, p38 can phosphorylate RNA-binding proteins, which can stabilize cytokine mRNA and thus amplify cytokine production. AP1, activating protein-1; ERK, extracellular signal-regulated kinases; MEK, MAPK/ERK kinase; SRE, serum response element.