2013 journal article
A Myristoylated Alanine-Rich C Kinase Substrate-Related Peptide Suppresses Cytokine mRNA and Protein Expression in LPS-Activated Canine Neutrophils
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 48(3), 314–321.
author keywords: MARCKS; cytokine; inflammation; neutrophil
MeSH headings : Animals; Dogs; Humans; Interleukin-8 / biosynthesis; Interleukin-8 / genetics; Interleukin-8 / metabolism; Intracellular Signaling Peptides and Proteins / metabolism; Lipopolysaccharides / pharmacology; Membrane Proteins / metabolism; Myristoylated Alanine-Rich C Kinase Substrate; Neutrophils / drug effects; Neutrophils / metabolism; Peptides / metabolism; Peptides / pharmacology; RNA, Messenger / biosynthesis; RNA, Messenger / genetics; Tumor Necrosis Factor-alpha / biosynthesis; Tumor Necrosis Factor-alpha / genetics; Tumor Necrosis Factor-alpha / metabolism
TL;DR:
Observations identify MARCKS protein as a promising therapeutic target in the treatment of inflammatory diseases or syndromes attributed to neutrophil influx and inflammatory cytokine production, such as sepsis, acute lung injury, and acute respiratory distress syndrome.
(via Semantic Scholar)
europepmc.org (repository)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: August 6, 2018
Myristoylated alanine-rich C kinase substrate (MARCKS) is a ubiquitously expressed protein kinase C substrate that has emerged as a potential therapeutic target for the amelioration of mucin secretion and inflammation in patients with chronic obstructive pulmonary disease. MARCKS also plays a key role in regulating the adhesion, migration, and degranulation of neutrophils. Moreover, given its biological role in epithelial and immune cells, we hypothesized that MARCKS may play an integral role in cytokine secretion by neutrophils. Because the amino terminus of MARCKS is highly conserved across vertebrate species, we successfully applied the well-characterized human MARCKS inhibitory peptide, myristoylated N-terminal sequence (MANS), to attenuate the function of MARCKS in isolated canine neutrophils. Pretreatment of canine neutrophils with MANS peptide significantly reduced both mRNA and protein expression in a broad range of LPS-induced cytokines, including IL-8, a chemokine (C-X-C motif) ligand-1 orthologue, and TNF-α, in comparison with untreated cells or those treated with a control peptide. This reduction in cytokine expression was observed even when neutrophils were treated with MANS 2 hours after LPS exposure. The observed reduction in cytokine secretion was not attributable to protein retention or cell death, but was associated with reduced cytokine transcript synthesis. These observations identify MARCKS protein as a promising therapeutic target in the treatment of inflammatory diseases or syndromes attributed to neutrophil influx and inflammatory cytokine production, such as sepsis, acute lung injury, and acute respiratory distress syndrome.