Regulation of P-Glycoprotein in Renal Proximal Tubule Epithelial Cells by LPS and TNF-α

Figure 6

Scheme illustrating the proposed sequence of events by which inflammatory mediators increase P-gp-mediated transport in GERP cells. (a) NO-dependent pathway after exposure to LPS directly or indirectly via TLR4. (b) NO-independent pathway after exposure to TNF-α. This pathway involves the activation of NF-κB inducing kinase (NIK) by TNF receptor associated factor family (TRAF) 2 and, consequently, the activation of NF-κB or the activation of TLR4 leading to the activation of IKK𝛽 by TRAF2 and consequently the activation of NF-κB. TIR; toll-IL-1R domain in TLR, LRR, leucine rich repeats domain in TLR.