Gap junctions in IL-1β-mediated cell survival response to strain
| Autor: | Albert J. Banes, Donald K. Bynum, Jie Qi, Liqun Chi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Strain (chemistry)
Cell Survival Physiology medicine.medical_treatment Interleukin-1beta Gap junction Connective tissue Connexin Fibroblasts Biology Mechanotransduction Cellular Cell junction Cell biology Tendons medicine.anatomical_structure Cytokine Elastic Modulus Physiology (medical) Immunology medicine Humans Stress Mechanical Cells Cultured Cell survival Homeostasis |
| Zdroj: | Journal of Applied Physiology. 110:1425-1431 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.00477.2010 |
| Popis: | Mechanical stimuli play important roles in proliferation and differentiation of connective tissue cells, and development and homeostatic maintenance of tissues. However, excessive mechanical loading to a tissue can injure cells and disrupt the matrix, as occurs in tendinopathy. Tendinopathy is a common clinical problem in athletes and in many occupational settings due to overuse of the tendon. Moreover, interleukin (IL)-1β is generally considered to be a “bad” cytokine, activating NF-κb and cell death and inducing matrix metalloproteinase (MMPs 1, 2, 3) expression and matrix destruction. However, activated NF-κB can also drive a cell survival pathway. We have reported that cyclic strain induced tenocyte death in three-dimensional (3D) cultures, and IL-1β could promote cell survival under strain. Therefore, it was hypothesized that 1) cyclic strain could induce cell death in tenocytes as observed in pathologic tendons in vivo; 2) a gene expression profile indicative of tendinopathy could be identified; and 3) low-dose IL-1β could protect cells from strain-induced, tendinopathy-like changes. Human tenocytes were cultured in 3D type I collagen hydrogels and subjected to 3.5% elongation at 1 Hz for 1 h/day for up to 5 days with or without IL-1β. Real-time RT-PCR data showed that cyclic strain regulated the expression of tendinopathy marker genes in a manner similar to that found in pathological tendons from patients and that addition of IL-1β reversed the gene expression changes to control levels. Results of further studies showed that IL-1β may modulate cell survival through upregulating the expression of connexin 43, which is involved in the modulation of cell death/survival in a variety of cells and tissues. The elucidation of the mechanisms underlying strain-induced cell death and recovery from strain injury will facilitate our understanding of the pathogenesis of tendinopathy and may lead to the discovery of new molecular targets for early diagnosis and treatment of tendinopathy. |
| Databáze: | OpenAIRE |
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