Oxidized phospholipids exert a dual effect on bile acid-induced CCL2 expression in pancreatic acini.

BACKGROUND: oxidized phospholipids (oxPLs) generated in inflammatory diseases could play a key role by inducing pro- and anti-inflammatory effects. OBJETIVES: we investigated the effect of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and oxidized POPC (oxPOPC) in the inflammatory response triggered in pancreatic acini.

METHODS: control acini were incubated in the absence or presence of either POPC or oxPOPC (≤100 μM). In additional experiments, oxPOPC effects were evaluated in sodium taurocholate (NaTc)-treated acini. CCL2 and TLR4 mRNA expression was analyzed by RT-qPCR. By western blot, JNK-MAPK, JAK and IκBα in cytoplasm as well as p65-NF-kB and p-STAT3 in the nucleus were evaluated. The involvement of TLR4, JNK-MAPK, JAK as well as NF-kB, STAT3 and PPARγ was assessed using pharmacological inhibition.

RESULTS: no effect was found in response to POPC. Conversely, in response to oxPOPC (10 μM), JNK-MAPK and JAK acted as TLR4-downstream signals, leading to CCL2 upregulation mainly through NF-kB activation. Moreover, TLR4 non-dependent mechanisms induced STAT3 activation in oxPOPC-treated acini. Mediated by PPARγ, oxPOPC (50 μM) inhibited the CCL2 overexpression found in NaTc-treated acini.

CONCLUSIONS: oxPOPC exerts pro- and anti-inflammatory effects in pancreatic acinar cells mediated by TLR4 and PPARγ signals, respectively. This dual action proved to be dependent on the concentration. The molecular mechanisms involved in the oxPL response could be useful for new therapeutic approaches to the treatment of oxPLs-related inflammatory pathologies.