Targeting MARCKS phosphorylation site domain shows therapeutic potential for allergic asthma

Abstract

Abstract Prevalence of asthma is increased all over the world, especially in Taiwan, study analyzed data of 997,729 enrolees from the National Health Insurance register from 2000 to 2007, the prevalence of asthma increase from 2.9% to 11.9%. Various signaling pathways and mechanisms have been identified and targeted for therapeutic application. Among them, one treatment, based on the use of MANS peptide, which is corresponding to the myristoylated N-terminal 24-amino acid portion of the MARCKS (myristoylated alanine-rich C kinase substrates) protein, to compete MARCKS’ binding to membrane has produced useful results. There is a lack of information regarding to the level/activity of phosphorylated MARCKS (p-MARCKS) in allergic asthma. It is also unclear if this activity can be directly suppressed for the allergic asthma treatment application. In this study, we have found elevated p-MARCKS in most of asthmatic tissues from human as well as from the animal model. This elevation can be directly suppressed by a peptide, MPS, targeting MARCKS phosphorylation site domain, prior to allergen sensitization. In addition, MPS pre-treatment also suppressed all of the symptoms associated with allergic airway asthma, which includes a reduction of inflammatory cells influx and TH2 cytokine presence in the lumen, and also a reduction of airway mucous cell metaplasia and airway hyperreactivity. In addition to inhibition of TH2 responses, lung dendritic cells migrate to mediastinal lymph nodes also decreased by MPS treatment. These results suggest that MARCKS phosphorylation site domain is a potential therapeutic target for the treatment of allergic asthma.