Disruption of monocyte-macrophage differentiation and trafficking by a heme analog during active inflammation.

ABSTRACT: Heme metabolism is a key regulator of inflammatory responses. Cobalt protoporphyrin IX (CoPP) is a heme analog and mimic that potently activates the NRF2/heme oxygenase-1 (HO-1) pathway, especially in monocytes and macrophages. We investigated the influence of CoPP on inflammatory responses using a murine model of colitis. Surprisingly, conditional deletion of myeloid HO-1 did not impact the colonic inflammatory response or the protective influence of CoPP in the setting of dextran sodium sulfate-induced colitis. Rather, we reveal that CoPP elicits a contradictory shift in blood myeloid populations relative to the colon during active intestinal inflammation. Major population changes include markedly diminished trafficking of CCR2⁺Ly6C^hi monocytes to the inflamed colon

SUBMITTER: Schaefer REM 

PROVIDER: S-EPMC8881314 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature