Summary
A bioRxiv preprint reports that MK2-deficient mice had more persistent colonic inflammation after chemical injury and produced fewer pro-resolving lipid mediators. Giving these mediators during recovery improved several measures of healing in the mice.
A bioRxiv preprint reports that MAPKAP kinase-2 (MK2) helps coordinate the resolution of colonic inflammation in mice. In a model of chemically induced intestinal injury, mice lacking MK2 developed more persistent inflammation and had lower levels of specialized pro-resolving mediators (SPMs), a group of lipid signals that help bring inflammatory responses toward resolution and tissue repair.
The researchers also found that administering SPMs during recovery improved weight, disease activity and mucosal healing in MK2-deficient mice. The findings point to a role for MK2 beyond its established involvement in promoting inflammatory signals: in this model, it was also linked to the processes that help inflammation subside.
MK2 deficiency disrupted recovery after colonic injury
The researchers induced colonic injury with dextran sodium sulfate (DSS), then compared the course of inflammation in mice with and without MK2. MK2-deficient mice experienced more severe and persistent inflammation, with continued production of pro-inflammatory cytokines and chemokines. They also had prolonged accumulation of neutrophils, immune cells that can contribute to tissue injury, and impaired recruitment of macrophages during recovery.
A similar impairment in resolution occurred when MK2 deficiency was restricted to myeloid cells, a group that includes several types of immune cell. This result points to a contribution from myeloid MK2 signaling in the recovery process.
Pro-resolving lipid mediators were reduced
Using lipid mediator metabololipidomics, the team found that colons in MK2-deficient mice did not make the usual transition from pro-inflammatory to pro-resolving lipid mediators. Levels of SPMs—including resolvins and lipoxins—were markedly reduced.
When the researchers administered SPMs during the recovery phase, the deficient mice showed improved weight, disease activity and mucosal healing. This intervention links the reduced mediator levels to impaired recovery in the mouse model, although the abstract does not specify the doses or the size of the effects.
The findings broaden the picture of MK2 signaling: inflammation involves not only the initial response to injury but also the processes that resolve it. Because the experiments used DSS-induced injury in mice, they provide preclinical evidence rather than evidence of a treatment effect in people with inflammatory bowel disease. The report is a bioRxiv preprint.