Of prime importance is the NF-κB pathway, which plays a cardinal role in mediating tissue inflammation in response to pathogen infection, physical insults, and proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) (Jobin and Sartor, 2000).
The organ also plays an important role in storing and releasing certain types of immune cells that mediate tissue inflammation.
EP4 receptor, a subtype of PGE2 receptors, mediates tissue inflammation and hypersensitivity.
Furthermore, several recent reports have shown that IL-21 is expressed at much higher levels in Th17 cells, a distinct Th lineage that is thought to mediate tissue inflammation [3], [8], [9], [10].
Recent evidence demonstrates that IL-21 is a key cytokine involved in the generation of Th17 cells which have been shown to mediate tissue inflammation via production of IL-17 [ 37, 38].
Recently, newly identified Th17 cells, distinct from Th1 and Th2 cells, were shown to produce IL-17, IL-17F, IL-22, and IL-21, and mediate tissue inflammation (Harrington et al., 2006; Park et al., 2005).
Interestingly (as in SLE), we found not only direct T cell-mediated tissue inflammation but also B cell hyperreactivity and autoantibody production, which also fosters the idea that Tregs are important for maintaining peripheral tolerance against B cell-mediated autoimmunity.
Moreover, oxidative stress mediated tissue damage may trigger inflammation and fibrosis in liver of CCl4 treated rats.
The SLPI has previously been reported to be upregulated in arthritic joints and to mediate tissue destruction and inflammation in a rat model of arthritis induced by intraperitoneal injection of SCW [ 26].
