Leukotriene B 4 at low dosage negates the catabolic effect of prostaglandin E 2 in human patellar tendon fibroblasts

Abstract

Tendinopathy often involves inflammation and matrix degeneration. The inflammatory mediators such as prostaglandin E 2 (PGE 2) and leukotriene B 4 (LTB 4) are implicated in the development of tendinopathy. Therefore, the purpose of this study was to determine the effect of PGE 2 and LTB 4 on the proliferation of human patellar tendon fibroblasts (HPTFs), the gene expression of collagen type I, MMP-1 and MMP-3, as well as the protein secretion of these gene products by the cells. The results showed that LTB 4 at low doses (0.1 and 1 nM) significantly increased cell proliferation compared to controls and LTB 4 at 0.1 nM negated the PGE 2-induced decrease in cell proliferation. In addition, PGE 2 at 100 ng/ml significantly increased the expression of MMP-1 and MMP-3 at both mRNA and protein levels. These stimulatory effects were significantly diminished by co-treatment with LTB 4 at 0.1 nM. Finally, neither PGE 2 nor LTB 4 treatment affected collagen type I gene expression. These results suggest that low levels of LTB 4 counterbalance the negative effects mediated by PGE 2 on tendon fibroblast proliferation and MMP production, which may lead to matrix degradation. Thus, our findings suggest that although LTB 4 is generally thought to be pathogenic, low levels of LTB 4 are actually beneficial in maintaining tendon tissue homeostasis.