German cockroach proteases regulate matrix metalloproteinase-9 in human bronchial epithelial cells

Area of Science:

• Immunology
• Environmental Health
• Molecular Biology

Background:

• Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in bronchial asthma pathogenesis.
• Elevated MMP-9 levels are observed in asthmatic patients' respiratory samples.
• German cockroach exposure is a known asthma risk factor, prompting investigation into its effects on MMP-9.

Purpose of the Study:

• To investigate the role of German cockroach fecal remnants (frass) in modulating MMP-9 expression.
• To elucidate the molecular mechanisms underlying cockroach frass-induced MMP-9 production.

Main Methods:

• Human bronchial epithelial cells were treated with cockroach frass and tumor necrosis factor-alpha (TNFα).
• MMP-9 mRNA, protein, and activity were quantified using RT-PCR, ELISA, and zymography.
• Involvement of serine proteases, protease-activated receptor-2 (PAR-2), extracellular signal-regulated kinase (ERK), and AP-1 was assessed using specific inhibitors and activators.

Main Results:

• Cockroach frass potentiated TNFα-induced MMP-9 expression via active serine proteases, independent of endotoxin.
• Frass increased ERK phosphorylation, and ERK inhibition attenuated MMP-9 induction.
• Activation of PAR-2 by frass or a specific peptide (SLIGKV) mimicked these effects, increasing MMP-9 and ERK phosphorylation.
• Both frass and SLIGKV enhanced AP-1 translocation and DNA binding.

Conclusions:

• German cockroach frass contains active serine proteases that augment TNFα-induced MMP-9 expression.
• The mechanism involves the activation of PAR-2, leading to ERK phosphorylation and AP-1 activation.