{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang CN"],"funding":["Ministry of Science and Technology"],"pagination":["1122-1134"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6451065"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["176(8)"],"pubmed_abstract":["<h4>Background and purpose</h4>Myristoylated alanine-rich C kinase substrate (MARCKS), a PKC substrate, facilitates mucus production and neutrophil migration. However, the effects of therapeutic procedures targeting the phosphorylation site of MARCKS on steroid-resistant asthma and the mechanisms underlying such effects have not yet been investigated. We designed a peptide that targets the MARCKS phosphorylation site (MPS peptide) and assessed its therapeutic potential against steroid-resistant asthma.<h4>Experimental approach</h4>Mice were sensitized with ovalbumin (OVA), alum, and challenged with aerosolized OVA five times a week for 1 month. The mice were intratracheally administered MPS peptides three times a week, 1 hr before OVA challenge. Asthma symptoms and cell profiles in the bronchoalveolar lavage were assessed, and key proteins were analysed using Western blotting.<h4>Key results</h4>Phosphorylated (p)-MARCKS was highly expressed in inflammatory and bronchial epithelial cells in OVA-immunized mice. MPS peptide reduced eosinophils, neutrophils, mucus production, collagen deposition, and airway hyper-responsiveness. Dexamethasone (Dexa) did not alleviate steroid-resistant asthma symptoms. MPS peptide caused a decrease in p-MARCKS, nitrotyrosine and the expression of oxidative stress enzymes, NADPH oxidase dual oxidase 1 and inducible NOS, in lung tissues. Compared to Dexa, MPS peptides inhibited C5a production and attenuated IL-17A and KC production in the airway more effectively, thus suppressing asthma symptoms.<h4>Conclusions and implications</h4>Our findings indicate that targeting MARCKS phosphorylation through MPS treatment may inhibit neutrophilic inflammation and relieve asthma symptoms, thereby highlighting its potential as a therapeutic agent for steroid-resistant asthma."],"journal":["British journal of pharmacology"],"pubmed_title":["Targeting the phosphorylation site of myristoylated alanine-rich C kinase substrate alleviates symptoms in a murine model of steroid-resistant asthma."],"pmcid":["PMC6451065"],"funding_grant_id":["MOST 106‐2320‐B‐039‐007","MOST 103‐2320‐B‐039‐022‐MY3"],"pubmed_authors":["Lin YC","Chang BC","Wang CN","Wu R","Lee CC","Chen CH"],"additional_accession":[]},"is_claimable":false,"name":"Targeting the phosphorylation site of myristoylated alanine-rich C kinase substrate alleviates symptoms in a murine model of steroid-resistant asthma.","description":"<h4>Background and purpose</h4>Myristoylated alanine-rich C kinase substrate (MARCKS), a PKC substrate, facilitates mucus production and neutrophil migration. However, the effects of therapeutic procedures targeting the phosphorylation site of MARCKS on steroid-resistant asthma and the mechanisms underlying such effects have not yet been investigated. We designed a peptide that targets the MARCKS phosphorylation site (MPS peptide) and assessed its therapeutic potential against steroid-resistant asthma.<h4>Experimental approach</h4>Mice were sensitized with ovalbumin (OVA), alum, and challenged with aerosolized OVA five times a week for 1 month. The mice were intratracheally administered MPS peptides three times a week, 1 hr before OVA challenge. Asthma symptoms and cell profiles in the bronchoalveolar lavage were assessed, and key proteins were analysed using Western blotting.<h4>Key results</h4>Phosphorylated (p)-MARCKS was highly expressed in inflammatory and bronchial epithelial cells in OVA-immunized mice. MPS peptide reduced eosinophils, neutrophils, mucus production, collagen deposition, and airway hyper-responsiveness. Dexamethasone (Dexa) did not alleviate steroid-resistant asthma symptoms. MPS peptide caused a decrease in p-MARCKS, nitrotyrosine and the expression of oxidative stress enzymes, NADPH oxidase dual oxidase 1 and inducible NOS, in lung tissues. Compared to Dexa, MPS peptides inhibited C5a production and attenuated IL-17A and KC production in the airway more effectively, thus suppressing asthma symptoms.<h4>Conclusions and implications</h4>Our findings indicate that targeting MARCKS phosphorylation through MPS treatment may inhibit neutrophilic inflammation and relieve asthma symptoms, thereby highlighting its potential as a therapeutic agent for steroid-resistant asthma.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Apr","modification":"2026-04-30T10:34:26.289Z","creation":"2025-02-18T22:56:51.043Z"},"accession":"S-EPMC6451065","cross_references":{"pubmed":["30706455"],"doi":["10.1111/bph.14596"]}}