Caspase-1 and IL-1β processing in a teleost fish

Area of Science:

• Immunology
• Molecular Biology
• Comparative Genomics

Background:

• Interleukin-1β (IL-1β) is a key pro-inflammatory cytokine central to immune responses.
• Mammalian IL-1β is processed by caspase-1, but this cleavage site is absent in non-mammalian vertebrates.
• Fish caspase-1 orthologues exist, yet their processing and activity remain largely uncharacterized.

Purpose of the Study:

• To investigate the auto-processing and activity of sea bass caspase-1.
• To identify alternatively spliced variants of caspase-1 in sea bass.
• To determine the cleavage sites of sea bass and avian IL-1β by caspase-1.

Main Methods:

• Biochemical assays to study sea bass caspase-1 auto-processing and activity.
• Molecular cloning and sequencing to identify caspase-1 variants.
• In vitro cleavage assays to map IL-1β processing sites.

Main Results:

• Sea bass caspase-1 auto-processing mirrors human enzyme activity, forming active heterodimers.
• Alternatively spliced variants of sea bass caspase-1 were identified.
• Sea bass and avian IL-1β are cleaved by caspase-1 at distinct, conserved aspartate residues, differing from mammalian sites.

Conclusions:

• Fish caspase-1 exhibits functional similarities to its mammalian counterpart.
• The evolution of caspase-1 isoforms suggests a conserved regulatory role in inflammation.
• Differential IL-1β cleavage sites in fish and birds highlight evolutionary divergence in inflammatory pathways.