It is noteworthy that the expression of PPAR is a known end-point of PPAR activation ; however, the effect of a PPAR pan-agonist on gastric tissue has been shown here for the first time. Furthermore, we have shown that the cytoprotective effect of LYSO-7 is dependent on PPAR��, as the in vivo antagonism of the receptor by GW9962 abolished the inhibitory action of LYSO-7 in Et/HCl-induced ulcers. These data corroborate the notion that the �� isoform seems to be the main class of PPAR in gastric tissue. It is worth mentioning that GW9962 has been previously used to determine the PPAR agonistic activity of newly synthesized compounds and to clarify the mechanisms of action of PPAR��. Neutrophil influx has been observed in several models of gastric ulcers, and they have been thought to act as an inducer of the harmful MK-4827 process. The participation of neutrophils in acute Et/HCl-induced gastric lesions in mice was shown here, as they rapidly accumulated in the injured tissue and in vivo neutrophil depletion significantly reduced the injured area. Together, these data corroborate the idea that inhibition of neutrophil recruitment may be a target for anti-gastric ulcer therapy, and that this can be modulated by LYSO-7 treatment. The role of PPAR activation on neutrophil influx has been shown in different models of inflammation, and the majority of them show an inhibitory effect on the process. The mechanisms involve the direct inhibition of leukocyteendothelial interactions and chemotaxis or impaired chemotactic mediator secretion. Our data show, for the first time, that a PPAR agonist affects the trafficking of neutrophils from the bone marrow, as LEE011 gastric-injured mice pretreated with LYSO-7 presented higher and lower numbers of neutrophils in the bone marrow and blood, respectively. Our previous results indicate that LYSO-7 may act directly on the locomotory functions of neutrophils. N-formyl-l-methionyl-lleucyl- l-phenylalanine -induced leukocyte-endothelial interactions in the mesenteric microcirculation are impaired in LYSO-7 treated rats, depending on reduced gene and protein expression of the CD62L and CD18 adhesion molecules by neutrophils. The results obtained in the present study contribute to this evidence, as the inhibitory effect on neutrophil trafficking was not dependent on NO mediation. The reduced neutrophil influx into gastric lesion caused by LYSO-7 was not modified by in vivo L-NAME treatment. In contrast, maintenance of the surface mucosal microcirculatory blood flow by LYSO-7 treatment occurred via NO mediation, and seemed to be dependent on reduced and increased protein expression of iNOS and eNOS, respectively. A beneficial role of NO on gastric ulcers has been shown, as the in vivo blockade of both eNOS and iNOS favors the development of gastric lesions and treatments with NO donors heal lesions.