How do we reconcile the apparently contradictory roles of TLRs in the development of intestinal inflammation? It is possible that there may be cross talk between various TLR family members in the maintenance of intestinal inflammation, and the balance between intestinal homeostasis versus intestinal injury may be a reflection of the relative balance between TLRs and their associated signaling molecules. Alternatively, different TLRs within the intestine may be more or less susceptible to upregulation by different physiological stressors. We and others also have shown that intestinal mucosal TLR expression varies in different parts of the GI tract (SC Gribar and DJ Hackam, unpublished report) (95), which could explain in part the regional effects of TLR signaling on intestinal inflammation that is observed. It also may be possible that unique, epithelialspecific, intracellular signaling networks are activated by specific TLR ligation in enterocytes. Additional studies designed to delineate the precise interaction between the various enterocyte TLRs and their downstream receptors are required to resolve these possibilities.