In addition, activation of PAR1 receptors with specific agonists administered systemically results in plasma extravasation in the rat bladder due to release of SP from terminal afferents. Our current results suggest that one component of PAR1-mediated bladder inflammation may be release of MIF from urothelial cells and MIF upregulation. Bladder/urothelial MIF upregulation during inflammation is a consistent finding regardless of the initiating inflammatory stimulus. We have demonstrated that released MIF is pro-inflammatory since blocking MIF or receptors for MIF reduce morphological and physiological signs of cystitis as well as decrease bladder production of pro-inflammatory cytokines, including MIF. Therefore, thrombin may activate PAR1 receptors in the urothelium to elicit MIF release from urothelial cells and thus continue and/or augment inflammation in the bladder. We showed previously that substance P elicits MIF release from the bladder in general, and urothelium in particular, dependent on bladder nerve activation. Therefore, it is possible that intravesical thrombin may also be functioning in a similar manner to elicit MIF release. Our results with intravesical lidocaine + thrombin treatment indicates that a considerable portion of MIF released is due to non-neurogenic mechanisms. We consider it a likely explanation that direct stimulation of MIF and PAR1 containing cells in the urothelium is involved in thrombinstimulated MIF release in the rat bladder. In fact, our earlier results investigating MIF release during neurogenic inflammation showed that intravesical lidocaine abolished MIF release in that model, and thus are different from findings in the present study. These observations suggest that there may be two components to MIF release, one a neurogenic component Paclitaxel involving SP release and a direct mechanism involving PAR1 stimulation of urothelial cells. Blocking activation of PAR1 receptors, blocking MIF or receptors for MIF should thus lead to decreased bladder inflammation. The role of quorum sensing in the adaptation and colonization of bacterial pathogens has been of increasing interest over the last decade. A growing body of evidence suggests that the direct sensing of threshold levels of various quorum sensing compounds is associated with changes in gene regulation resulting in altered phenotypic expression of virulence factors.. Examples of such changes include regulation of adherence, motility, toxin production and expression of type three secretion systems in a variety of bacterial species.. While the quorum sensing mechanisms of Gram-positive bacteria are often associated with the production and sensing of modified peptide signals, the autoinducers of Gram-negative bacteria are more commonly acylhomoserine lactones. Another form of quorum-sensing, mediated by autoinducer-2, has been described as a highly conserved inter-species mechanism of communication with genetic conservation over a large number of both Gram.