4.7 Article

14-3-3 modulation of the inflammatory response

Journal

PHARMACOLOGICAL RESEARCH
Volume 163, Issue -, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2020.105236

Keywords

14-3-3 protein; Inflammation; Chronic inflammatory condition; Autoimmune disease; Respiratory disease; Protein-protein interaction

Funding

  1. H2020 Marie Sklodowska-Curie Actions of the European Commission [675179]
  2. Marie Curie Actions (MSCA) [675179] Funding Source: Marie Curie Actions (MSCA)

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The 14-3-3 proteins play crucial roles in regulating the inflammatory response at genetic, molecular, and cellular levels. They affect key components of the immune response and can lead to clinical syndromes when their recognition processes are disrupted. Abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.
Regulation of inflammation is a central part of the maintenance of homeostasis by the immune system. One important class of regulatory protein that has been shown to have effects on the inflammatory process are the 14-3-3 proteins. Herein we describe the roles that have been identified for 14-3-3 in regulation of the inflammatory response. These roles encompass regulation of the response that affect inflammation at the genetic, molecular and cellular levels. At a genetic level 14-3-3 is involved in the regulation of multiple transcription factors and affects the transcription of key effectors of the immune response. At a molecular level many of the constituent parts of the inflammatory process, such as pattern recognition receptors, protease activated receptors and cytokines are regulated through phosphorylation and recognition by 14-3-3 whilst disruption of the recognition processes has been observed to result in clinical syndromes. 14-3-3 is also involved in the regulation of cell proliferation and differentiation, this has been shown to affect the immune system, particularly T- and B cells. Finally, we discuss how abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.

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