title: Kinin generation from exogenous kininogens at the surface of retinoic acid-differentiated human neuroblastoma IMR-32 cells after stimulation with interferon-γ.
abstract: Bradykinin-related peptides, kinins, ubiquitously occur in the nervous system and together with other pro-inflammatory mediators contribute to pathological states of that tissue such as edema and chronic pain. In the current work we characterized the kinin-forming system of neuronal cells obtained by differentiation of human neuroblastoma cell line IMR-32 with retinoic acid. These cells were shown to concentrate exogenous kinin precursors, kininogens, on the surface, release kinins from kininogens and subsequently convert kinins to their des-Arg metabolites. Significantly higher amounts of kinins and des-Arg-kinins were produced after cell stimulation with interferon-γ, a potent pro-inflammatory mediator involved in many neurological disorders. The expression of the major tissue kininogenase (the human kallikrein 1) and the major cell membrane-bound kininase (the carboxypeptidase M) also increased after cell stimulation with interferon-γ, suggesting the involvement of these enzymes in the kinin production and degradation, respectively. Interferon-γ was also able to up-regulate the expression of two known subtypes of kinin receptors. On the protein level, the changes were only observed in the expression of the des-Arg-kinin-specific type 1 receptor which functions in the propagation of the inflammatory state. Taken together, these results suggest a novel way for local kinin and des-Arg-kinin generation in the nervous tissue during pathological states accompanied by interferon-γ release.
authors.affiliation: Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland. ibeth.guevara-lora@uj.edu.pl
authors.forename: Ibeth
authors.initials: I
authors.lastname: Guevara-Lora
authors.forename: Magdalena
authors.initials: M
authors.lastname: Majkucinska
authors.forename: Anna
authors.initials: A
authors.lastname: Barbasz
authors.forename: Alexander
authors.initials: A
authors.lastname: Faussner
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D007704:Kininogens / Q000378:metabolism* / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011485:Protein Binding; D011869:Radioligand Assay; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins; D020840:Tissue Kallikreins / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D058851:GPI-Linked Proteins; D007704:Kininogens; D043783:Receptor, Bradykinin B1; D011994:Recombinant Proteins; D014212:Tretinoin; D007371:Interferon-gamma; C058479:carboxypeptidase M; D020840:Tissue Kallikreins; D008666:Metalloendopeptidases; D001920:Bradykinin