Clinical relevance of understanding mitogen-activated protein kinases involved in asthma

ABSTRACT

Introduction: Mitogen-activated protein kinases (MAPKs) are a large family of evolutionary conserved intracellular enzymes that play a pivotal role in signaling pathways mediating the biologic actions of a wide array of extracellular stimuli.

Areas covered: MAPKs are implicated in most pathogenic events involved in asthma, including both inflammatory and structural changes occurring in the airways. Indeed, MAPKs are located at the level of crucial convergence points within the signal transduction networks activated by many cytokines, chemokines, growth factors, and other inducers of bronchial inflammation and remodeling such as immunoglobulin E (IgE) and oxidative stress.

Expert opinion: Therefore, given the growing importance of MAPKs in asthma pathobiology, these signaling enzymes are emerging as key intracellular pathways whose upstream activation can be inhibited by biological drugs such as anti-cytokines and anti-IgE.

KEYWORDS:

• Asthma
• MAPKs
• JNK
• ERK
• p38
• MAPK inhibitors

Article Highlights

• MAPKs play a key role in intracellular signal transduction.

• MAPKs are remarkably involved in activation of immune/inflammatory cells.

• MAPKs significantly affect the functions of airway structural cells.

• MAPK activation contributes to the pathobiology of airway inflammation and remodeling underlying asthma.

• Upstream inhibition of several triggers of MAPK activation participates in the mechanisms of action of anti-asthma biological drugs.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.