Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching.

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 B(4) and the expression of 5-lipoxygenase; and (2) the production level of leukotriene B(4) is inversely related to that of prostaglandin E(2).

STUDY DESIGN

Controlled laboratory study.

METHODS

Human patellar tendon fibroblasts were uniaxially stretched in the presence of indomethacin (25 micro M) or MK-886 (10 micro M). After stretching for 4 hours, followed by 4 hours rest, levels of prostaglandin E(2), leukotriene B(4), and expression of 5-lipoxygenase were measured.

RESULTS

Stretched tendon fibroblasts increased the levels of leukotriene B(4) but did not appreciably change the expression of 5-lipoxygenase. Indomethacin decreased the cellular production of prostaglandin E(2) but caused increased leukotriene B(4) levels. MK-886 caused decreased production of leukotriene B(4) but increased production of prostaglandin E(2).

CONCLUSIONS

Cyclic stretching of human tendon fibroblasts increases the production of prostaglandin E(2) and leukotriene B(4). Blocking prostaglandin E(2) production leads to increased leukotriene B(4) 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 B(4) within the tendon, potentially contributing to the development of tendinopathy.