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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/C432    most recent 00085.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kim, H. G. Articles by Chung, D. K. PubMed PubMed Citation Articles by Kim, H. G. Articles by Chung, D. K.

RECEPTORS AND SIGNAL TRANSDUCTION

Mechanical stress induces tumor necrosis factor- production through Ca²⁺ release-dependent TLR2 signaling

¹Graduate School of Biotechnology and Institute of Life Science and Resources and ²Skin Biotechnology Center, Kyung Hee University, Yongin; and ³Division of Cardiology, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea

Submitted 14 February 2008 ; accepted in final form 4 June 2008

We studied centrifugation-mediated mechanical stress-induced tumor necrosis factor- (TNF-) production in the monocyte-like cell line THP-1. The induction of TNF- by mechanical stress was dependent on the centrifugation speed and produced the highest level of TNF- after 1 h of stimulation. TNF- production returned to normal levels after 24 h of stimulation. Mechanical stress also induced Toll-like receptor-2 (TLR2) mRNA in proportion to the expression of TNF-. The inhibition of TLR2 signaling by dominant negative myeloid differentiation factor 88 (MyD88) blocked TNF- expression response to mechanical stress. After transient overexpression of TLR2 in HEK-293 cells, mechanical stress induced TNF- mRNA production. Interestingly, mechanical stress activated the c-Src-dependent TLR2 phosphorylation, which is necessary to induce Ca²⁺ fluxes. When THP-1 cells were pretreated with BAPTA-AM, thapsigargin, and NiCl₂·6H₂O, followed by mechanical stimulation, both TLR2 and TNF- production were inhibited, indicating that centrifugation-mediated mechanical stress induces both TLR2 and TNF- production through Ca²⁺ releases from intracellular Ca²⁺ stores following TLR2 phosphorylation. In addition, TNF- treatment in THP-1 cells induced TLR2 production in response to mechanical stress, whereas the preincubation of anti-TNF- antibody scarcely induced the mechanical stress-mediated production of TLR2, indicating that TNF- produced by mechanically stimulated THP-1 cells affected TLR2 production. We concluded that TNF- production induced by centrifugation-mediated mechanical stress is dependent on MyD88-dependent TLR2 signaling that is associated with Ca²⁺ release and that TNF- production induced by mechanical stress affects TLR2 production.

centrifugation; Toll-like receptor; THP-1 cells