Cyclic stretch regulates immune responses via tank‐binding kinase 1 expression in macrophages

Macrophages distributed in tissues throughout the body contribute to homeostasis. In the inflammatory state, macrophages undergo mechanical stress that regulates the signal transduction of immune responses and various cellular functions. However, the effects of the inflammatory response on macrophages under physiological cyclic stretch are unclear. We found that physiological cyclic stretch suppresses inflammatory cytokine expression in macrophages by regulating NF‐κB activity. NF‐κB phosphorylation at Ser536 in macrophages was inhibited, suggesting that tank‐binding kinase (TBK1) regulates NF‐κB activity during physiological stress. Moreover, TBK1 expression was suppressed by physiological stretch, and TBK1 knockdown by siRNA induced the suppression of NF‐κB phosphorylation at Ser536. In conclusion, physiological stretch triggers suppression of a TBK1‐dependent excessive inflammatory response, which may be necessary to maintain tissue homeostasis.

[1]  Fangfang Zhou,et al.  The Crosstalk Between Hippo-YAP Pathway and Innate Immunity , 2020, Frontiers in Immunology.

[2]  C. Leifer,et al.  Molecular regulation of TLR signaling in health and disease: mechano-regulation of macrophages and TLR signaling , 2020, Innate immunity.

[3]  R. Zhou,et al.  DAMP-sensing receptors in sterile inflammation and inflammatory diseases , 2019, Nature Reviews Immunology.

[4]  Hsien-Da Huang,et al.  Mechanical stretch induces hair regeneration through the alternative activation of macrophages , 2019, Nature Communications.

[5]  C. Doerschuk,et al.  Myeloid TBK1 Signaling Contributes to the Immune Response to Influenza , 2019, American journal of respiratory cell and molecular biology.

[6]  E. Nemoto,et al.  Mechanical regulation of macrophage function - cyclic tensile force inhibits NLRP3 inflammasome-dependent IL-1β secretion in murine macrophages , 2019, Inflammation and regeneration.

[7]  Chungho Kim,et al.  Cellular machinery for sensing mechanical force , 2018, BMB reports.

[8]  Yuntian Chen,et al.  Physiological stretch induced proliferation of human urothelial cells via integrin α6‐FAK signaling pathway , 2018, Neurourology and urodynamics.

[9]  P. Wenzel,et al.  Mechanical stretch on endothelial cells interconnects innate and adaptive immune response in hypertension. , 2018, Cardiovascular research.

[10]  S. Dupont,et al.  Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction. , 2016, Experimental cell research.

[11]  I. Amit,et al.  Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment , 2014, Cell.

[12]  C. Kirkpatrick,et al.  In vitro investigation of silica nanoparticle uptake into human endothelial cells under physiological cyclic stretch , 2014, Particle and Fibre Toxicology.

[13]  T. Ross,et al.  Integrins in mechanotransduction. , 2013, Current opinion in cell biology.

[14]  P. Pavasant,et al.  Mechanical stress-induced interleukin-1beta expression through adenosine triphosphate/P2X7 receptor activation in human periodontal ligament cells. , 2013, Journal of periodontal research.

[15]  Stanley J Stachelek,et al.  Correlating macrophage morphology and cytokine production resulting from biomaterial contact. , 2013, Journal of biomedical materials research. Part A.

[16]  S. Akira,et al.  Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. , 2011, Immunity.

[17]  S. Akira,et al.  The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors , 2010, Nature Immunology.

[18]  B. Chain,et al.  Quantitative imaging assay for NF-κB nuclear translocation in primary human macrophages , 2008, Journal of immunological methods.

[19]  S. Akira,et al.  TLR signaling. , 2006, Current topics in microbiology and immunology.

[20]  Mone Zaidi,et al.  Molecular regulation of mechanotransduction. , 2005, Biochemical and biophysical research communications.

[21]  Leonard Buckbinder,et al.  NF-kappaB RelA phosphorylation regulates RelA acetylation. , 2005, Molecular and cellular biology.

[22]  Peter G. Gillespie,et al.  Molecular basis of mechanosensory transduction , 2001, Nature.

[23]  J D Hellums,et al.  Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells. , 2000, American journal of physiology. Heart and circulatory physiology.

[24]  H. Sakurai,et al.  IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain. , 1999, The Journal of biological chemistry.