Title:Novel Therapeutic Potential of Mitogen-Activated Protein Kinase Activated Protein Kinase 2 (MK2) in Chronic Airway Inflammatory Disorders
VOLUME: 20 ISSUE: 4
Author(s):Rakesh Kumar Singh* and Abul Kalam Najmi
Affiliation:Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi-110062, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi-110062
Keywords:Mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK2 or MK2), inflammation, inflammatory
airway disease, p38MAPK pathway, chronic lung inflammation, MK2 inhibitors, asthma.
Abstract:Objective: The primary focus of this review is to highlight the current and emerging proinflammatory
role of MK2 kinase signaling in p38MAPK pathway and to provide a detailed evaluation
on the prospects of MK2 inhibition with special emphasis on the etiology of chronic inflammatory
airway diseases, such as asthma, idiopathic pulmonary fibrosis, lung cancer, acute lung injury and
acute respiratory distress syndrome.
Background: MK2 belongs to serine-threonine kinase family and is activated directly by stress and
inflammatory signal through p38MAPK phosphorylation in diverse inflammatory conditions through
the Toll-like receptor signaling pathway. MK2 has been thought to be a critical factor involved in the
regulation of synthesis and release of pro-inflammatory (TNF-α, IL-6 and IL-1β, etc.) proteins. Targeted
inhibition of MK2 kinase has been shown to significantly reduce the production and release of
these cytokine molecules. Therefore, MK2 has been identified as an effective strategy (alternative to
p38MAPK) to block this pro-inflammatory signaling pathway.
Results: The inhibition of MK2 may lead to similar or better efficacy as that of p38 inhibitors, and interestingly
avoids the systemic toxicity shown by the p38 inhibitors. Thus, MK2 has been the focus of
intense interdisciplinary research and its specific inhibition can be a novel and potential therapeutic
strategy for the treatment of chronic airway inflammatory diseases.
Conclusion: Promising advancement in understanding and rigorous exploration of the role of MK2
kinase in inflammatory processes may contribute to the development of newer and safer therapy for
the treatment of chronic airway inflammatory diseases in the future.
