Interleukin 12 on extracellular matrix-related factors and functional characteristics of equine endometrial fibroblasts

Context Tissue fibrosis is described as the excessive accumulation of extracellular matrix (ECM) components. This process is associated with inflammation, and the interaction between fibroblasts and immune cells plays a key role, driving the progression of fibrosis. Results of recent study suggest that interleukin (IL)-12 may play a role in the processes associated with the development of fibrosis. This proinflammatory cytokine is synthesized and released by macrophages, dendritic cells, and B cells. Aims The objective of this study was to determine: (i) the expression of IL-12 and its receptor in different mare endometrial categories; (ii) the effects of IL-12 on the expression of ECM-related factors; and (iii) endometrial fibroblast functional characteristics. Methods The mRNA expression of IL-12 subunits and IL-12 receptor was determined using quantiative polymerase chain reaction (qPCR). The expression of ECM-related factors and functional characteristics in endometrial fibroblasts were determined using qPCR, Western blotting, zymography with bromodeoxyuridine and scratch assays. Key results IL-12Rβ2 mRNA expression was upregulated in category IIB endometrium during the mid-luteal phase compared with the follicular phase of the estrous cycle. The IL-12 treatment of endometrial fibroblasts increased mRNA expression of COL1A1, COL3A1, ACTA2, and LOXL2, as well as matrix metalloproteinase (MMP)-9 and MMP3, with elevated pro-MMP2 and MMP9 gelatinolytic activity. Moreover, IL-12 reduced fibroblast proliferation after 96 h, without effect on migration. Conclusions The findings indicate that IL-12 has a direct impact on the mRNA expression of fibrotic markers, MMP-2 and MMP-9 gelatinolytic activity and fibroblast proliferation. Implications This suggests a potential role for IL-12 in the processes associated with ECM remodeling.