Role of p38-mitogen-activated protein kinase in COPD: pathobiological implications and therapeutic perspectives

ABSTRACT

Introduction: The p38 serine-threonine kinases are members of the large family of mitogen-activated protein kinases (MAPK). In particular, p38 MAPK subgroup includes four isoforms (α, β, γ, δ), among which p38α and p38β are mainly involved in inflammatory disorders. Indeed, by activating key transcription factors and by inducing the expression of several cytokines and chemokines, p38α plays a central role in the pathobiology of chronic obstructive pulmonary disease (COPD).

Areas covered: This concise review focuses on the contribution of p38 MAPK to development, maintenance, and amplification of chronic lung inflammation in COPD. Moreover, we discuss the potential role of p38 MAPK as suitable target for perspective therapeutic approaches under evaluation as potential new COPD treatments. In this regard, an extensive literature search has been conducted throughout PubMed source (1990–2020).

Expert opinion: Despite some promising preclinical data, so far the results of clinical trials evaluating p38 MAPK inhibitors have been quite disappointing, thus suggesting a cautious judgment about the future perspectives of these drugs for COPD therapy.

KEYWORDS:

• COPD
• lung inflammation
• p38 MAPK
• p38 inhibitors

Article highlights

• p38 MAPK plays a key role in signaling mechanisms underlying COPD pathobiology.

• Phosphorylated p38 MAPK is overexpressed in lung immune/inflammatory cells of COPD patients.

• p38 MAPK significantly contributes to decrease corticosteroid responsiveness in COPD patients.

• Experimental p38 MAPK inhibitors are under clinical investigation for potential COPD treatment.

• Pharmacological inhibition of p38 MAPK could contribute to restore corticosteroid responsiveness in COPD patients.

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.