TLR Signalling Pathways Diverge in Their Ability to Induce PGE₂

Figure 6

Mechanisms of PGE₂ production by TLR family members. TLR4 triggering induces the transcription of COX2 via NF-κB and MAPK p38 and ERK1/2 as well as cPLA₂ phosphorylation and AA mobilization, presumably via MAPK and/or MSK1, which is in turn converted into PGE₂ by COX2 and released into the medium. Similar mechanisms of action can be envisaged when TLR7 and 8 are concomitantly activated by R848. TLR3, TLR5, and TLR7 fail to activate NF-κB and selected MAPKs, thus hindering the transcription of COX2. By contrast, TLR1/2 and TLR2/6 cause no PGE₂ release because of inefficient cPLA₂ phosphorylation and AA mobilization, which may correlate with their inability to phosphorylate MSK1.