A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

A novel intrinsically disordered outer membrane lipoprotein of Aggregatibacter actinomycetemcomitans binds various cytokines and plays a role in biofilm response to interleukin-1β and interleukin-8




TekijätTuuli Ahlstrand, Heidi Tuominen, Arzu Beklen, Annamari Torittu, Jan Oscarsson, Raija Sormunen, Marja T. Pöllänen, Perttu Permi, Riikka Ihalin

KustantajaTaylor & Francis

Julkaisuvuosi2017

JournalVirulence

Vuosikerta8

Numero2

Aloitussivu115

Lopetussivu134

Sivujen määrä20

ISSN2150-5594

DOIhttps://doi.org/10.1080/21505594.2016.1216294

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/16839697


Tiivistelmä
Intrinsically disordered proteins (IDPs) do not have a well-defined and
stable three-dimensional fold. Some IDPs can function as either
transient or permanent binders of other proteins and may interact with
an array of ligands by adopting different conformations. A novel outer
membrane lipoprotein, bacterial interleukin receptor I (BilRI) of the
opportunistic oral pathogen Aggregatibacter actinomycetemcomitans binds a
key gatekeeper proinflammatory cytokine interleukin (IL)-1β. Because
the amino acid sequence of the novel lipoprotein resembles that of
fibrinogen binder A of Haemophilus ducreyi, BilRI could have the
potential to bind other proteins, such as host matrix proteins. However,
from the tested host matrix proteins, BilRI interacted with neither
collagen nor fibrinogen. Instead, the recombinant non-lipidated BilRI,
which was intrinsically disordered, bound various pro/anti-inflammatory
cytokines, such as IL-8, tumour necrosis factor (TNF)-α, interferon
(IFN)-γ and IL-10. Moreover, BilRI played a role in the in vitro sensing
of IL-1β and IL-8 because low concentrations of cytokines did not
decrease the amount of extracellular DNA in the matrix of bilRI- mutant
biofilm as they did in the matrix of wild-type biofilm when the biofilms
were exposed to recombinant cytokines for 22 hours. BilRI played a role
in the internalization of IL-1β in the gingival model system but did
not affect either IL-8 or IL-6 uptake. However, bilRI deletion did not
entirely prevent IL-1β internalization, and the binding of cytokines to
BilRI was relatively weak. Thus, BilRI might sequester cytokines on the
surface of A. actinomycetemcomitans to facilitate the internalization
process in low local cytokine concentrations.


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