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Antimicrobial activity does not predict cytokine response to adrenomedullin or its shortened derivatives.

Hussain QA, Sheehan BE, McKay IJ, Allaker RP - Mediators Inflamm. (2007)

Bottom Line: However, exposure to fragments compared to whole AM resulted in reduced production of these cytokines (60% mean reduction at 24 hours, P<.001).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Dentistry, Queen Mary, University of London, Newark Street, London E1 2AT, UK.

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.

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Related in: MedlinePlus

IL-1β response of FIBcells after a 24-hour exposure to AM and fragments (mean ± SD;  = 6). AM and individual fragments were each added to cultured cells at a final concentration of 10-9 g/mL. Antimicrobial fragments (16-52, 22-52, 34-52, and 13-52). Nonantimicrobial fragments (26-52, 16-21, 1-12, and 1-21).
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fig2: IL-1β response of FIBcells after a 24-hour exposure to AM and fragments (mean ± SD; = 6). AM and individual fragments were each added to cultured cells at a final concentration of 10-9 g/mL. Antimicrobial fragments (16-52, 22-52, 34-52, and 13-52). Nonantimicrobial fragments (26-52, 16-21, 1-12, and 1-21).

Mentions: Cells were exposed to AM and individual fragments at a concentration of 10-9 g/mL.A time-dependent increase in the release of IL-1α and IL-1β with exposure to AMand eight shortened derivatives was observed. Treatment with AMresulted in a significant increase in IL-1α and IL-1β at 4 hours ( < .001and < .05, resp.), 8 hours ( < .001), and 24 hours ( < .001)in comparison to controls. Treatment with all fragments resulted in asignificant increase in both IL-1α and IL-1β at 24 hours ( < .001) incomparison to controls. Significant increases were also observed at 8 hourswith the exception of the IL-1α response to fragment 1-12 and the IL-1βresponses to fragments 1-12, 1-21, and 22-52. All fragments showed a significantlydecreased response for both cytokines in comparison to the whole molecule at both8 hours, with the exception of the IL-1α response to fragment 1-12, and 24 hours(60% overall meanreduction, < .001). Responsesat 24 hours to AM and individual peptides are shown in Figures 1 and 2. No consistent differences were demonstrated between the cytokine response elicitedby the antimicrobial and nonantimicrobial fragments. IL-6and IL-8 were produced by the cells; however, levels did not changesignificantly with time or peptide tested (all levels < 140 pg/mL).


Antimicrobial activity does not predict cytokine response to adrenomedullin or its shortened derivatives.

Hussain QA, Sheehan BE, McKay IJ, Allaker RP - Mediators Inflamm. (2007)

IL-1β response of FIBcells after a 24-hour exposure to AM and fragments (mean ± SD;  = 6). AM and individual fragments were each added to cultured cells at a final concentration of 10-9 g/mL. Antimicrobial fragments (16-52, 22-52, 34-52, and 13-52). Nonantimicrobial fragments (26-52, 16-21, 1-12, and 1-21).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2233874&req=5

fig2: IL-1β response of FIBcells after a 24-hour exposure to AM and fragments (mean ± SD; = 6). AM and individual fragments were each added to cultured cells at a final concentration of 10-9 g/mL. Antimicrobial fragments (16-52, 22-52, 34-52, and 13-52). Nonantimicrobial fragments (26-52, 16-21, 1-12, and 1-21).
Mentions: Cells were exposed to AM and individual fragments at a concentration of 10-9 g/mL.A time-dependent increase in the release of IL-1α and IL-1β with exposure to AMand eight shortened derivatives was observed. Treatment with AMresulted in a significant increase in IL-1α and IL-1β at 4 hours ( < .001and < .05, resp.), 8 hours ( < .001), and 24 hours ( < .001)in comparison to controls. Treatment with all fragments resulted in asignificant increase in both IL-1α and IL-1β at 24 hours ( < .001) incomparison to controls. Significant increases were also observed at 8 hourswith the exception of the IL-1α response to fragment 1-12 and the IL-1βresponses to fragments 1-12, 1-21, and 22-52. All fragments showed a significantlydecreased response for both cytokines in comparison to the whole molecule at both8 hours, with the exception of the IL-1α response to fragment 1-12, and 24 hours(60% overall meanreduction, < .001). Responsesat 24 hours to AM and individual peptides are shown in Figures 1 and 2. No consistent differences were demonstrated between the cytokine response elicitedby the antimicrobial and nonantimicrobial fragments. IL-6and IL-8 were produced by the cells; however, levels did not changesignificantly with time or peptide tested (all levels < 140 pg/mL).

Bottom Line: However, exposure to fragments compared to whole AM resulted in reduced production of these cytokines (60% mean reduction at 24 hours, P<.001).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Dentistry, Queen Mary, University of London, Newark Street, London E1 2AT, UK.

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.

Show MeSH
Related in: MedlinePlus