title: A CCL chemokine-derived peptide (CDIP-2) exerts anti-inflammatory activity via CCR1, CCR2 and CCR3 chemokine receptors: Implications as a potential therapeutic treatment of asthma.
abstract: Allergic asthma is a chronic inflammatory disease characterized by the accumulation of eosinophils, Th2 cells and mononuclear cells in the airways, leading to changes in lung architecture and subsequently reduced respiratory function. We have previously demonstrated that CDIP-2, a chemokine derived peptide, reduced in vitro chemotaxis and decreased cellular infiltration in a murine model of allergic airway inflammation. However, the mechanisms involved in this process have not been identified yet. Now, we found that CDIP-2 reduces chemokine-mediated functions via interactions with CCR1, CCR2 and CCR3. Moreover, using bone marrow-derived eosinophils, we demonstrated that CDIP-2 modifies the calcium fluxes induced by CCL11 and down-modulated CCR3 expression. Finally, CDIP-2 treatment in a murine model of OVA-induced allergic airway inflammation reduced leukocyte recruitment and decreases production of cytokines. These data suggest that chemokine-derived peptides represent new therapeutic tools to generate more effective antiinflammatory drugs.
authors.affiliation: CBRL, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico; Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Méndez-Enríquez
authors.affiliation: CBRL, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico; Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Medina-Tamayo
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Soldevila
authors.affiliation: Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico.
authors.forename: T I
authors.initials: TI
authors.lastname: Fortoul
authors.affiliation: Laboratorio de Neurobiología Molecular y Neuroquímica de Adicciones, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México, D.F., México.
authors.forename: B
authors.initials: B
authors.lastname: Anton
authors.affiliation: Departmento de Biología Celular, CINVESTAV-IPN, México, D.F., Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Flores-Romo
authors.affiliation: CBRL, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico; Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico. Electronic address: garciaze@servidor.unam.mx.
authors.forename: E A
authors.initials: EA
authors.lastname: García-Zepeda
mesh_terms: D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000187:drug effects; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011014:Pneumonia / Q000188:drug therapy / Q000473:pathology; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism*; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000473:pathology
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; C529302:CDIP-2 peptide; D016207:Cytokines; D010455:Peptides; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D010047:Ovalbumin; D002118:Calcium
keywords: Allergic airway inflammation; CCL13/MCP-4; CCR3; Chemokine receptors; Chemokines; Chemotaxis