More importantly, TLR4 signaling can also upregulate other TLRs, such as TLR2, and thus amplify the inflammatory responses. Although TLR2 is predominantly expressed in the first-line host defense cells (monocytes, macrophages, dendritic cells and PMN) (65, 66) , its expression is low in ECs and epithelial cells (67) . Studies from our laboratory showed that LPS through TLR4-and MyD88-dependent signaling induced TLR2 upregulation in ECs (68) . We have demonstrated that TLR4 signaling, through activating NF-κB, upregulates TLR2 expression in ECs, and this process is enhanced by oxidant signaling generated by PMN NAD(P)H oxidase. The functional relevance of NAD(P)H oxidase in mediating TLR4-induced TLR2 expression in ECs is evident by markedly elevated and stable ICAM-1 expression as well as augmented PMN migration in response to sequential challenge with LPS and peptidoglycan (68) . Thus, TLR2 activation, signaled by TLR4 and as regulated by PMN NAD(P)H oxidase, is an important mechanism responsible for amplifying PMN transmigration to sites of infection ( Figure 3 ).