Christina A Christianson1, Rafeul Alam. 1. Division of Allergy and Immunology, Department of Medicine, National Jewish Health and University of Colorado Denver, Denver, Colorado 80206, USA.
Abstract
PURPOSE OF REVIEW: The role of immunological memory formation focusing upon Th2 inflammatory responses in asthma is well supported and reviewed previously. Here, we review data supporting the establishment of a tissue-based signalling memory utilizing examples of in-vitro, in-vivo and clinical reports of sustained extracellular signal regulated kinase 1/2 (ERK1/2) activation in asthma. RECENT FINDINGS: Endosomal recycling of receptors contributes to chronic signalling activation, presumably through increased receptor availability. This chronic signalling constitutes a bistable state and the formation of a tissue memory. The transition to chronic asthma is marked by the persistence of low-level disease severity and chronic signalling in the apparent absence of an environmental trigger. SUMMARY: System bistability provides a mathematical explanation for a tissue-based memory. We will have to generate quantitative data about the involved biochemical reactions (substrates, products, dissociation constants of the reactions) to utilize this model. Only then will we be able to understand and interfere with a tissue memory-driven disease and curtail the persistence of asthma.
PURPOSE OF REVIEW: The role of immunological memory formation focusing upon Th2 inflammatory responses in asthma is well supported and reviewed previously. Here, we review data supporting the establishment of a tissue-based signalling memory utilizing examples of in-vitro, in-vivo and clinical reports of sustained extracellular signal regulated kinase 1/2 (ERK1/2) activation in asthma. RECENT FINDINGS: Endosomal recycling of receptors contributes to chronic signalling activation, presumably through increased receptor availability. This chronic signalling constitutes a bistable state and the formation of a tissue memory. The transition to chronic asthma is marked by the persistence of low-level disease severity and chronic signalling in the apparent absence of an environmental trigger. SUMMARY: System bistability provides a mathematical explanation for a tissue-based memory. We will have to generate quantitative data about the involved biochemical reactions (substrates, products, dissociation constants of the reactions) to utilize this model. Only then will we be able to understand and interfere with a tissue memory-driven disease and curtail the persistence of asthma.
Authors: Fernanda P R Santana; Rafael C da Silva; Simone Dos S Grecco; Aruanã J M C R Pinheiro; Luciana C Caperuto; Fernanda M Arantes-Costa; Samuel R Claudio; Kelly Yoshizaki; Mariângela Macchione; Daniel A Ribeiro; Iolanda F L C Tibério; Lídio G Lima-Neto; João H G Lago; Carla M Prado Journal: Mediators Inflamm Date: 2019-09-03 Impact factor: 4.711