Probiotic bacteria Escherichia coli Nissle (EcN) was shown to prevent or heal acute murine colitis, but gastroprotective effects of EcN against mucosal injury have been little studied. In this study, the effects of EcN on formation of stress-induced gastric erosions were assessed in rats. Rats were divided in following treatment groups: 1) vehicle (control); 2) EcN 10(1) CFU/ml; 3) EcN 10(4) CFU/ml and 4) EcN 10(8) CFU/ml. One hour after treatment, the rats were exposed to 3.5 h of water immersion and restraint stress (WRS) and then sacrificed. Involvement of prostaglandins was tested using indomethacin given one hour before EcN, whereas that of sensory nerves was assessed using neurotoxic dose of capsaicin in rats pretreated with EcN or vehicle. The expression of proinflammatory cytokine (IL-1beta), ghrelin, peroxisome proliferator receptor gamma (PPARgamma) and heat-shock protein (HSP70) was assessed by RT-PCR and Western blot. Exposure to WRS in vehicle-pretreated rats induced acute erosions. Pretreatment with EcN significantly reduced WRS lesions and increased gastric blood flow. This protective effect was completely abolished by indomethacin and significantly attenuated by capsaicin-denervation. The exposure to WRS was accompanied by an increase in gastric mucosal expression of IL-1beta, ghrelin, PPARgamma, HSP70 and COX-2. In rats pretreated with EcN, a significant downregulation of mRNA and protein expression for IL-1beta, COX-2 and PPARgamma and increased expression of HSP70 without major change in activation of NFkappaB were observed. We conclude that EcN protects gastric mucosa against WRS erosions due to antiinflammatory and vasodilatory actions involving HSP70, prostaglandins and sensory afferent neurons.