Research Article
Collagen Induced Arthritis in DBA/1J Mice Associates with Oxylipin Changes in Plasma
Figure 4
A systematic autoimmune activation in RA. Appearance of proinflammatory cytokines (IL-1β and IL-6, TNFα) as well as the appearance of ROS in RA. The cytokines normally induce the apoptosis via the caspase pathway but also inhibit apoptosis through degradation IκB activating nuclear factor-κB (NF-κB), which consequently translocate to the nucleus upregulating the antiapoptotic genes (BcL2 and BcL-xL). The activated NF-κB then can also further enhance the production of proinflammatory cytokines and chemokines as well as COX-II enzyme. (b) Upregulated oxylipin response. During RA increased levels of AA derived prostaglandins and HETEs are detected. 8- and 12-HETE are able to activate NF-κB exasperating RA. Due to increased levels of ROS, DHA derived peroxidation products are also found. (c) Dysregulated anti-inflammatory response. LA derived oxylipins including HODEs, KODEs, TriHOMEs, DiHOMEs, and EpOMEs are ligands of peroxisome proliferator-activated receptor- (PPAR-) γ. Due to decreased levels of these anti-inflammatory oxylipins, the ability of PPAR-γ to inhibit the activation of NF-κB and indirectly affect apoptosis is diminished.