LPS-induced MMP-9 expression is mediated through the MAPKs-AP-1 dependent mechanism in BEAS-2B and U937 cells

Area of Science:

• Cellular and Molecular Biology
• Immunology
• Respiratory Medicine

Background:

• Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).
• Mitogen-activated protein kinases (MAPKs) are key signaling molecules involved in cellular responses to inflammatory stimuli.

Purpose of the Study:

• To investigate the role of MAPKs in lipopolysaccharide (LPS)-induced MMP-9 secretion in human bronchial epithelial (BEAS-2B) and macrophage-like (U937) cells.
• To elucidate the signaling pathways involved in LPS-induced MMP-9 expression.

Main Methods:

• Cell viability was assessed using MTT assays.
• U937 cells were differentiated into macrophages using phorbol 12-myristate 13-acetate (PMA).
• Cells were pretreated with MAPK inhibitors (ERK1/2, JNK, p38) and stimulated with LPS. Protein and RNA expression, cytokine production, and DNA binding activity were measured using Western blotting, qRT-PCR, ELISA, and DNA binding assays.

Main Results:

• LPS stimulation significantly increased MMP-9 expression and secretion in both cell types.
• Inhibitors of stress-activated protein kinase/jun kinase (SAPK/JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) completely blocked LPS-induced MMP-9.
• LPS-induced transactivation of activator protein-1 (AP-1) was inhibited by JNK and ERK1/2 inhibitors.

Conclusions:

• LPS activates ERK1/2 and JNK pathways, leading to AP-1 activation and subsequent MMP-9 expression in BEAS-2B and U937 cells.
• ERK1/2 and JNK inhibitors demonstrate potential therapeutic value for COPD treatment by suppressing MMP-9.
• Targeting the ERK1/2 and JNK signaling pathways could be a viable strategy for managing COPD.