title: A recombinant cystatin from Ascaris lumbricoides attenuates inflammation of DSS-induced colitis.
abstract: Helminthiasis may ameliorate inflammatory diseases, such as inflammatory bowel disease and asthma. Information about immunomodulators from Ascaris lumbricoides is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We evaluated the immunomodulatory effects of a recombinant cystatin from A. lumbricoides on an acute model of dextran sodium sulphate (DSS)-induced colitis in mice. From an A. lumbricoides cDNA library, we obtained a recombinant cystatin (rAl-CPI). Protease activity inhibition was demonstrated on cathepsin B and papain. Immunomodulatory effects were evaluated at two intraperitoneal doses (0.5 and 0.25 μg/G) on mice with DSS-induced colitis. Body weight, colon length, Disease Activity Index (DAI), histological inflammation score, myeloperoxidase (MPO) activity, gene expression of cytokines and cytokines levels in colon tissue were analysed. Treatment with rAl-CPI significantly reduced DAI, MPO activity and inflammation score without toxic effects. Also, IL-10 and TGF-B gene overexpression was observed in rAl-CPI-treated group compared to DSS-exposed control and healthy mice. Furthermore, a reduction in IL-6 and TNF-A expression was found, and this was confirmed by the levels of these cytokines in colonic tissue. In conclusion, rAl-CPI reduces inflammation in a mouse model of DSS-induced colitis, probably by increasing the expression of anti-inflammatory cytokines and reducing pro-inflammatory ones.
authors.affiliation: Institute for Immunological Research, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: S
authors.initials: S
authors.lastname: Coronado
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: L
authors.initials: L
authors.lastname: Barrios
authors.affiliation: Institute for Immunological Research, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: J
authors.initials: J
authors.lastname: Zakzuk
authors.affiliation: Institute for Immunological Research, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: R
authors.initials: R
authors.lastname: Regino
authors.affiliation: Institute for Immunological Research, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: V
authors.initials: V
authors.lastname: Ahumada
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: L
authors.initials: L
authors.lastname: Franco
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: Y
authors.initials: Y
authors.lastname: Ocampo
authors.affiliation: Institute for Immunological Research, Universidad de Cartagena, Cartagena, Colombia.
authors.forename: L
authors.identifier: 0000-0002-5204-1109
authors.initials: L
authors.lastname: Caraballo
mesh_terms: D000818:Animals; D017164:Ascaris lumbricoides / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000378:metabolism; D015891:Cystatins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000276:immunology; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
chemical_list: D015891:Cystatins; D016207:Cytokines; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016264:Dextran Sulfate
keywords: 
  Ascaris lumbricoides
  ; DSS-induced colitis; anti-inflammatory cytokines; cystatin