title: Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-beta production by galectin-9 homologues isolated from intestinal parasites.
abstract: We isolated a galectin-9 (Gal-9) homologue gene (Tl-gal) from an adult worm of the canine gastrointestinal nematode parasite, Toxascaris leonina, via random cDNA library sequencing. The deduced amino acid sequence of the Tl-gal genes evidenced an identity of 89% with the galectin of Dirofilaria immitis, 87% identity with the galectin of Brugia malayi, and 35% identity with the human GAL-9 gene. To evaluate immune modulate function of Tl-GAL in host inflammatory response, we constructed recombinant Tl-GAL (rTl-GAL) using an Escherichia coli expression vector system and treated to intestinal inflammation mice. Although the carbohydrate-binding ability of rTl-GAL was less than that of rat galectin, we confirmed that recombinant rTl-GAL has carbohydrate-binding activity. The clinical symptoms of dextran sulfate sodium (DSS)-treated mice after rTl-GAL pre-treatment were found to be minimized, or less profound, as compared to those of the rTl-GAL untreated group. Additionally, the DSS-treated mice exhibited a significant shortening of the colon, but the large intestines of the rTl-GAL pre-treated mice were longer than those of the control group (P<0.05). Additionally, the rTl-GAL treated group exhibited significantly increased the levels of TGF-beta and IL-10 (P<0.05). The production of these regulatory cytokines may ameliorate intestinal inflammation. These findings demonstrate that rTl-GAL could inhibit inflammation reactions via the inhibition of Th1 and Th2 cytokine production by increasing the production of TGF-beta and IL-10 cytokines. The rTl-GAL may induce TGF-beta expression, primarily via the activation of the p38 pathway. In conclusion, rTl-GAL may function like a host galectin, thus functioning as a regulatory molecule in the host immune system; rTl-GAL may prove useful in the design of novel therapeutic intervention strategies for the treatment of allergic and immune diseases.
authors.affiliation: Department of Parasitology, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 626-870, Republic of Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Cho
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Keun Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Soon Cheol
authors.initials: SC
authors.lastname: Ahn
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Hak Sun
authors.initials: HS
authors.lastname: Yu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D016264:Dextran Sulfate; D004751:Enteritis / Q000139:chemically induced / Q000473:pathology; D005260:Female; D037161:Galectins / Q000302:isolation & purification / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014114:Toxascaris / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018509:DNA, Helminth; D037161:Galectins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D016264:Dextran Sulfate