Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-I

Background: During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. Results: By using PMA-differentiated human monocyte cells line THP-I, we found that CD147 mediated matrix metalloproteinases (MMPs) expression of the leukemic THP-I cells and thus enhanced the invasiveness of THP-I cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-I cells ( 289.61 +/- 31.63) was higher than that of the undifferentiated THP-I cells ( 205.1 +/- 19.25). There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-I cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-I cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/ CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-I cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP2 in the differentiated THP-I cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-I cells was 41.82 % and 25.15%, respectively. Conclusion: The results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-I cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-I cells. The matured monocytes / macrophages, via their high expression of CD147, may play an important role in promoting the tissue repair or tissue damage during their inflammatory response.