Mitogen-activated protein kinase (MAPK)

The Mitogen-activated protein kinase (MAPK) signaling pathway is a fundamental intracellular signaling module that translates extracellular stimuli into diverse cellular responses. In airway inflammatory cells, such as macrophages, neutrophils, and T-lymphocytes, MAPK subfamilies—including p38, ERK, and JNK—play a pivotal role in regulating the production of pro-inflammatory cytokines and chemokines [Chung, 2011, PubMed: 21834165]. Activation of these kinases by environmental stressors, allergens, or pathogens leads to the phosphorylation of transcription factors that drive the expression of mediators like TNF-alpha and IL-8, which are central to the pathology of asthma and chronic obstructive pulmonary disease (COPD) [Mercado et al., 2014, PubMed: 24631644]. Consequently, MAPK components have been targeted by various small-molecule inhibitors designed to suppress chronic airway inflammation. While these drugs show potent anti-inflammatory effects in preclinical models, their clinical utility has been constrained by systemic side effects and the presence of redundant signaling pathways that can bypass specific kinase inhibition [Lomas et al., 2012, PubMed: 22496495]. Understanding the cell-specific roles of MAPK signaling remains crucial for developing more selective and effective therapeutic strategies for respiratory diseases.

Other names

MAP kinaseMitogen-activated protein kinase cascadeMAPK pathwayp38 MAPK signaling

Small molecule inhibition of kinase phosphorylation and catalytic activity, preventing the activation of downstream transcription factors (e.g., AP-1, NF-kappaB) and the subsequent synthesis of pro-inflammatory cytokines in airway immune cells [Chung, 2011, PubMed: 21834165; Mercado et al., 2014, PubMed: 24631644].