Pathological interplay of NF-κB and M1 macrophages in chronic inflammatory lung diseases

Abstract

Inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis depend on the pathology of the nuclear factor kappa B (NF-κB) signalling pathway and M1 macrophage polarization. This review discusses the intimate molecular interactions and processes that modulate NF-κB's promotion of M1 macrophages and chronic inflammation/tissue damage within the confines of this review. NF-κB activation in macrophages produces pro-inflammatory mediators (cytokines - TNFα, IL6, IL1β, and reactive oxygen species (ROS), further increasing airway remodeling and fibrosis. MAPK, JAK-STAT, and PI3K-Akt signalling systems cross-talked with the pathway, amplifying its effect on lung disease progression. Therapeutic strategies focused on inhibiting this axis, including inhibition of NF-κB and small molecule/modulation of macrophage polarization, represent potential ways to attenuate inflammation and promote tissue repair. The potential of precision medicine is illustrated by natural compounds such as curcumin and resveratrol and innovative RNA-based and nanoparticle delivery systems. Despite these challenges, specificity, minimizing systemic side effects, and optimized delivery methods remain difficult. To develop targeted therapies, more research must be conducted to refine targeted approaches, including immune profiling and single-cell analysis. This review aims to advance the management of hard-to-treat inflammatory lung diseases by addressing these complexities.

Keywords: Chemokine; Cytokine; Inflammation; Lung diseases; M1 macrophage; NF-kB; ROS.