Pavan Prabhala and
Alaina Ammit*
+Author Affiliations
- ↵* Corresponding author; email: alaina.ammit@sydney.edu.au
Abstract
Chronic inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are clinically and socio-economically important diseases globally. Currently the mainstay of anti-inflammatory therapy in respiratory diseases is corticosteroids.
Although corticosteroids have proven clinical efficacy in asthma, many asthmatic inflammatory conditions (e.g. infection, exacerbation, severe asthma) are not responsive to them. Moreover, despite an understanding that COPD progression is driven by inflammation we currently do not have effective anti-inflammatory strategies to combat this disease. Hence alternative anti-inflammatory strategies are required. The p38 MAPK pathway has been implicated as an important signalling pathway driving airway inflammation; hence pharmacological inhibitors against p38 MAPK may provide potential therapy in chronic respiratory disease. In this review we discuss some of the recent in vitro and in vivo studies targeting p38 MAPK to date, but suggest that p38 MAPK inhibitors may prove less effective than originally considered due to the fact that they may block anti-inflammatory molecules along with pro-inflammatory responses. We propose that an alternative strategy may be to target an anti-inflammatory molecule further downstream of p38 MAPK, i.e. tristetraprolin (TTP). TTP is a destabilising RNA binding protein that enhances mRNA decay of many proteins, including proteins implicated as playing a role in chronic respiratory diseases. We suggest that understanding the molecular mechanism of TTP expression and its temporal regulation will guide future development of novel anti-inflammatory pharmacotherapeutic approaches to combat respiratory disease.
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