Cerebral ischemia triggers inflammation and apoptosis, and the transcription factor NF-kappaB is a key regulator of both events. Here, we report on the induction of the peptidoglycan recognition protein-S (PGRP-S) in a mouse model of cerebral ischemia. Upregulation was reduced if the NF-kappaB subunit RelA was conditionally deleted in the brain. Regulation of PGRP-S transcription by RelA was confirmed in vitro. Cotransfection of a RelA expression plasmid stimulated the expression of a PGRP-S luciferase fusion gene. Mutation of two NF-kappaB response elements in the PGRP-S promoter disrupted stimulation by RelA. To investigate the function of PGRP-S in cerebral ischemia, we subjected PGRP-S(-/-) mice to cerebral ischemia. However, there was no difference in the infarct size in PGRP-S-deficient mice compared to controls. In summary, the data show that PGRP-S is induced in cerebral ischemia by RelA, but its role in ischemia is unclear.