Calpeptin attenuated apoptosis and intracellular inflammatory changes in muscle cells

Area of Science:

• Muscle cell biology
• Immunology
• Molecular medicine

Background:

• Idiopathic inflammatory myopathies (IIMs) involve chronic muscle inflammation.
• Extracellular inflammatory stimuli may trigger secondary intracellular changes in muscle cells.
• A self-sustaining inflammatory loop is implicated in IIM pathogenesis.

Purpose of the Study:

• To investigate the role of calpain, a calcium-sensitive protease, in mediating inflammatory responses within muscle cells.
• To determine if calpain activation bridges extracellular inflammatory signals to intracellular changes in muscle.
• To explore calpain inhibition as a potential therapeutic strategy for IIMs.

Main Methods:

• Rat L6 myoblast cells were treated with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α).
• Major histocompatibility complex class-I (MHC-I) expression and inflammation-related transcription factors were assessed.
• Calpain activation, apoptosis, and cyclooxygenase-2 (COX-2) expression were measured.
• The effect of calpeptin, a calpain inhibitor, on these cellular changes was evaluated.

Main Results:

• IFN-γ treatment induced MHC-I expression and activated key inflammation-related transcription factors (p-ERK1/2, NF-κB).
• TNF-α treatment induced apoptosis, activated calpain, and increased COX-2 expression.
• Subsequent treatment with calpeptin significantly attenuated the intracellular inflammatory and apoptotic changes induced by both IFN-γ and TNF-α.

Conclusions:

• Calpain activation plays a crucial role in mediating secondary inflammatory and apoptotic changes in muscle cells stimulated by extracellular inflammatory factors.
• Calpain inhibition effectively reduces these detrimental intracellular responses.
• These findings highlight calpain as a promising therapeutic target for managing idiopathic inflammatory myopathies.