Omeprazole induces apoptosis in normal human polymorphonuclear leucocytes.

Area of Science:

• Immunology
• Pharmacology
• Cell Biology

Background:

• Human polymorphonuclear neutrophils (PMN) play a crucial role in inflammatory responses.
• Omeprazole is a widely used proton pump inhibitor for treating acid-related gastrointestinal disorders.
• Understanding drug-induced cellular effects on immune cells is vital for therapeutic optimization.

Purpose of the Study:

• To investigate the in vitro induction of apoptosis in human PMN by omeprazole.
• To compare the apoptotic potential of native omeprazole (OM) and acidified omeprazole (OM-HCl).
• To elucidate the underlying molecular mechanisms of omeprazole-induced PMN apoptosis.

Main Methods:

• In vitro incubation of human PMN with varying concentrations and durations of OM and OM-HCl.
• Assessment of apoptosis using specific caspase inhibitors (caspase 3 and caspase 8 inhibitors).
• Evaluation of the role of cysteine cathepsin proteases and cellular sulfhydryl groups using specific inhibitors and thiol-containing molecules (beta-ME, GSH).

Main Results:

• Both OM and OM-HCl are potent inducers of PMN apoptosis in a time- and dose-dependent manner.
• OM-HCl demonstrated higher efficiency in inducing apoptosis compared to OM.
• Apoptosis induction is caspase-dependent, with OM-HCl uniquely involving caspase 8 and sulfhydryl group interactions.
• Cysteine cathepsins and cellular sulfhydryl groups are implicated in the apoptotic pathways activated by both drug forms.

Conclusions:

• Omeprazole, particularly its acidified form, induces apoptosis in human PMN through caspase-dependent pathways.
• OM-HCl's enhanced apoptotic effect may involve binding to cellular sulfhydryl groups.
• Omeprazole-induced PMN apoptosis could offer therapeutic benefits in managing gastric inflammatory conditions.