Inflammatory Response of Human Tendon Fibroblasts to Cyclic Mechanical Stretching

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Abstract
Background: The cellular and molecular mechanisms for the development of tendinopathy are not clear, but inflammatory mediators produced by tendon fibroblasts in response to repetitive mechanical loading may be an important factor. Hypotheses: (1) Cyclic stretching of tendon fibroblasts affects the production of leukotriene B4 and the expression of 5-lipoxygenase; and (2) the production level of leukotriene B4 is inversely related to that of prostaglandin E2. Study Design: Controlled laboratory study. Methods: Human patellar tendon fibroblasts were uniaxially stretched in the presence of indomethacin (25 μM) or MK-886 (10 μM). After stretching for 4 hours, followed by 4 hours rest, levels of prostaglandin E2, leukotriene B4, and expression of 5-lipoxygenase were measured. Results: Stretched tendon fibroblasts increased the levels of leukotriene B4 but did not appreciably change the expression of 5-lipoxygenase. Indomethacin decreased the cellular production of prostaglandin E2 but caused increased leukotriene B4 levels. MK-886 caused decreased production of leukotriene B4 but increased production of prostaglandin E2. Conclusions: Cyclic stretching of human tendon fibroblasts increases the production of prostaglandin E2 and leukotriene B4. Blocking prostaglandin E2 production leads to increased leukotriene B4 levels and vice versa. Clinical Relevance: The use of nonsteroidal anti-inflammatory drugs for the treatment of tendon inflammation might increase the levels of leukotriene B4 within the tendon, potentially contributing to the development of tendinopathy.