Lipid mediators (LMs) are bioactive lipids that have a significant impact on controlling acute inflammation. This research explores how macrophages, which produce LMs, change these molecules from a state that promotes inflammation to one that aids in resolution during acute kidney injury (AKI).
Acute kidney injury (AKI) often leads to a poor outcome, and as of now, there is no effective treatment available. It is vital to comprehend the processes that can hinder the progression of AKI. In the case of AKI, a type of immune cell called macrophages generates lipid mediators (LMs), which are critical in both stimulating and managing inflammation. Therefore, understanding how they function is of great importance.
This study concentrated on the transcription factor MAFB, known to influence the ability of macrophages to suppress inflammation. The researchers examined the role of macrophages in AKI. In experiments where AKI was induced in mice lacking MAFB in their macrophages (referred to as MAFB-deficient mice), the outcomes were worse compared to normal mice. A detailed analysis of gene expression in macrophages from the MAFB-deficient mice revealed a significant reduction in the gene ALOX15, which is a key enzyme for creating pro-resolving LMs. Additionally, it was found that the expression of MAFB in macrophages during AKI is influenced by a pro-inflammatory lipid mediator called PGE2, and in turn, MAFB regulates the expression of ALOX15 that is affected by PGE2. Altogether, these results suggest that MAFB is crucial for converting LMs from a state that promotes inflammation to one that encourages resolution.
Since the equilibrium between pro-inflammatory and pro-resolving LMs greatly influences the outcome of acute inflammation, the insights from this research are expected to aid in the creation of new therapeutic and diagnostic strategies for AKI and other acute inflammatory conditions.
This research was supported by grants from JSPS KAKENHI (Grants 19K07499 and 23K05586), the Strategic Basic Research Programs (JPMJPF2017), and the Program for Next Generation Researchers Challenging Research (JPMJSP2124).
