Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk


Apolinar Maya-Mendoza

Ostatnie publikacje
1.  Adamson A., Boddington C., Downton P., Rowe W., Bagnall J., Lam C., Maya-Mendoza A., Schmidt L., Harper Claire V.V., Spiller David G., Rand David A.A., Jackson Dean A., White Michael R. H.R., Paszek P., Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states, Nature Communications, ISSN: 2041-1723, DOI: 10.1038/ncomms12057, Vol.7, pp.12057-1-14, 2016

Cells respond dynamically to pulsatile cytokine stimulation. Here we report that single, or well-spaced pulses of TNFα (>100 min apart) give a high probability of NF-κB activation. However, fewer cells respond to shorter pulse intervals (<100 min) suggesting a heterogeneous refractory state. This refractory state is established in the signal transduction network downstream of TNFR and upstream of IKK, and depends on the level of the NF-κB system negative feedback protein A20. If a second pulse within the refractory phase is IL-1β instead of TNFα, all of the cells respond. This suggests a mechanism by which two cytokines can synergistically activate an inflammatory response. Gene expression analyses show strong correlation between the cellular dynamic response and NF-κB-dependent target gene activation. These data suggest that refractory states in the NF-κB system constitute an inherent design motif of the inflammatory response and we suggest that this may avoid harmful homogenous cellular activation.

Afiliacje autorów:
Adamson A. - inna afiliacja
Boddington C. - inna afiliacja
Downton P. - inna afiliacja
Rowe W. - inna afiliacja
Bagnall J. - inna afiliacja
Lam C. - inna afiliacja
Maya-Mendoza A. - inna afiliacja
Schmidt L. - inna afiliacja
Harper Claire V.V. - University of Manchester (GB)
Spiller David G. - inna afiliacja
Rand David A.A. - University of Warwick (GB)
Jackson Dean A. - inna afiliacja
White Michael R. H.R. - University of Manchester (GB)
Paszek P. - inna afiliacja

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