title: Antimicrobial activity does not predict cytokine response to adrenomedullin or its shortened derivatives.
abstract: The aim of this study was to investigate cytokine release from oral keratinocytes and fibroblasts in response to AM and shortened derivatives previously characterised in terms of their antimicrobial activities. Cells were incubated with AM or its fragments (residues 1-12, 1-21, 13-52, 16-21, 16-52, 22-52, 26-52, and 34-52), and culture supernatants collected after 1, 2, 4, 8, and 24 hours. A time-dependant increase in production of interleukin1-alpha and interleukin 1-beta from keratinocytes in response to all peptides was demonstrated. However, exposure to fragments compared to whole AM resulted in reduced production of these cytokines (60% mean reduction at 24 hours, P<.001). No consistent differences were shown between the cytokine response elicited by antimicrobial and nonantimicrobial fragments. The production of interleukin-6 and interleukin-8 did not change significantly with time or peptide used. Fibroblast cells were relatively unresponsive to all treatments. This study demonstrates that antimicrobial activity does not predict cytokine response to adrenomedullin or its shortened derivatives.
authors.affiliation: Institute of Dentistry, Queen Mary, University of London, Newark Street, London E1 2AT, UK.
authors.forename: Quratul Ann
authors.initials: QA
authors.lastname: Hussain
authors.forename: Barry E
authors.initials: BE
authors.lastname: Sheehan
authors.forename: Ian J
authors.initials: IJ
authors.lastname: McKay
authors.forename: Robert P
authors.initials: RP
authors.lastname: Allaker
mesh_terms: D053607:Adrenomedullin / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D005881:Gingiva / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D009061:Mouth Mucosa / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D051381:Rats; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D010455:Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; D053607:Adrenomedullin; C022616:thiazolyl blue