PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons.

Peroxisome proliferator-activated receptor-α (PPAR-α), a lipid activated transcription factor of nuclear hormone receptor superfamily, can relieve pain through a rapid-response mechanism. However, little is known about the underlying mechanism. Herein, we report that PPAR-α activation acutely inhibits the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglion (DRG) neurons. Pre-application of PPAR-α agonist GW7647 for 2 min decreased the amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner. GW7647 shifted the concentration-response curve for proton downwards, with a decrease of 36.9 ± 2.3% in the maximal current response to proton. GW7647 inhibition of proton-gated currents can be blocked by GW6471, a selective PPAR-α antagonist. Moreover, PPAR-α activation decreased the number of acidosis-evoked action potentials in rat DRG neurons. Finally, peripheral administration of GW7647 dose-dependently relieved nociceptive responses to injection of acetic acid in rats. These results indicated that activation of peripheral PPAR-α acutely inhibited functional activity of ASICs in a non-genomic manner, which revealed a novel mechanism underlying rapid analgesia through peripheral PPAR-α.

[Study on manufacturing materials of imitation snails].

OBJECTIVE: To make imitation snails by using substances with chemotaxis to Schistosoma japonicum miracidia. METHODS: The imitation snails were made by using Fe3+, gelatin and agar. The modified comparison method of Roberts was used to observe the chemotaxis of imitation snails and snail conditioned water (SCW) to Schistosoma japonicum miracidia. RESULTS: The mixture consisting of 0.1 or 0.5 mol/L Fe3+, 9% or 10% gelatin, and that consisting of 0.5 mol/L Fe3+, 9% gelatin, 2% or 1% agar could be used to make the imitation snails. The chemotaxis of imitation snails made by the mixtures above was stronger than that of SCW. CONCLUSION: The mixtures made by certain proportion of Fe3+, gelatin or gelatin and agar can be used to make imitation snails.

[Studies on mechanism of protective immunity against infection of Schistosoma japonicum induced by Sj26 gene transfected dendritic cell].

OBJECTIVE: To explore the mechanism of protective immunity against Schistosoma japonicum infection induced by Sj26 gene transfected dendritic cell (DC). METHODS: 48 BALB/c mice were divided randomly into 4 groups with 12 each. The mice were injected through auricle for three times with Sj26 gene transfected DC (Group A), pcDNA3 transfected DC (Group B), untreated DC (Group C) and RPMI-1640 (Group D) respectively, and challenged with 40+/-2 cercariae of S. japonicum per mouse 2 weeks after the last immunization. Sera from mice were examined for IgG antibody, IFN-gamma and IL-4 by ELISA. Western blot was used for detecting specific anti-Sj26 IgG antibody. The production of IFN-gamma and IL-4 in the supernatant of spleen cells stimulated with soluble egg antigen (SEA) and ConA was quantified by sandwich ABC-ELISA. The proliferation of spleen cells were measured with MTT method. RESULTS: IgG antibody increased significantly in the mice of group A at 2 weeks after the last immunization (absorbency A491=0.117), higher than that of group B (A491=0.061) and group C (A491=0.058) (P<0.05). The Mr 26000 antigen of S. japonicum was strongly recognized by sera from group A by Western blot. The level of IL-4 in mice of each group showed no significant difference before and after immunization. The level of IFN-gamma in group A (101.4+/-4.9 pg/ml) was significantly higher than that before immunization (15.0+/-1.9 pg/ml) and that of group B (40.1+/-3.1 pg/ml) and group C (35.6+/-1.2 pg/ml) (P<0.01). The level of IFN-gamma in spleen cells from group A in response to ConA and SEA (171.2 and 70.8 pg/ml, respectively) was higher than that of group D (91 and 49.7 pg/ml, respectively) (P<0.01). The level of IL-4 in spleen cells from group A in response to ConA and SEA (79.7 and 50.7 pg/ml, respectively) was lower than that of group D (125.2 and 70.5 pg/ml, respectively) (P<0.01). The stimulating index of spleen cells from group A was 4.1 and 2.82 in response to ConA and SEA respectively, higher than that of other groups (compared with group D, P<0.05). CONCLUSION: Sj26 gene transfected dendritic cell induces predominant Th1 type immune response which might play a role in protection against S. japonicum infection.

Comparison of the role of dendritic cells and macrophages in inducing protective immunity against Schistosoma japonicum.

OBJECTIVE: To compare a potential role of dendritic cells (DCs) and macrophages in inducing protective immunity against infection with Schistosoma japonicum. METHODS: DCs and macrophages were pulsed in vitro with soluble egg antigen (SEA) of S. japonicum. BALB/c mice were injected three times with DCs or macrophages, either antigen-pulsed or not, and challenged with 40 +/- 2 cercariae of S. japonicum per mouse. Worms were collected 42 days later by portal perfusion of the mice and egg number of liver was calculated. To evaluate whether protective immunity had been induced by preparations of DCs or macrophages, the worm burden and fertility (eggs per female per mouse liver) were compared between the groups of mice. The antibody level against SEA was detected by ELISA. RESULTS: With respect to mice injected with untreated cells, numbers of worms and eggs per female worms were significantly reduced in the groups of mice having received pulsed DCs (26. 3% and 37.9%, respectively), or pulsed macrophages (22.0% and 30.7%). Untreated DCs and macrophages induced no significant effects. The antibody level against SEA rose in sera of all groups of mice up to 42 days after the challenge, but most pronounced in those immunized with pulsed DCs, although this was not significantly different from other groups. CONCLUSION: The results suggest that the protective immunity against S. japonicum might be induced by DCs to a higher extent than by macrophages after in vitro pulsing with egg antigen.