Hypoxia suppresses stretch-induced elongation and orientation of macrophages

Oya, Koki; Sakamoto, Naoya; Sato, Masaaki

doi:10.3233/bme-130770

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Our results indicate that cyclic stretch plays an important role in preventing excessive inflammasome activation in mechanical environmental tissues ( Oya et al, 2013 ; Mennens et al, 2017 ), such as the lungs, heart, arterial wall, and periodontal ligament, in which the infiltration of large numbers of macrophages derived from peripheral blood monocytes occurs during the processes of inflammation and tissue repair. Of these tissues, the periodontal ligament, which is located between the tooth root and its surrounding bone ( Bartold, 2012 ), is subjected to mechanical stimuli, including cyclic stretch, from normal mastication.…”

Section: Discussionmentioning

confidence: 78%

Cyclic Stretch Negatively Regulates IL-1β Secretion Through the Inhibition of NLRP3 Inflammasome Activation by Attenuating the AMP Kinase Pathway

et al. 2018

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Macrophages are immune cells of hematopoietic origin that play diverse roles in host defenses and tissue homeostasis. In mechanical microenvironments, macrophages receive mechanical signals that regulate various cellular functions. However, the mechanisms by which mechanical signals influence the phenotype and function of macrophages in the process of inflammation have not yet been elucidated in detail. We herein examined the effects of cyclic stretch (CS) on NLR family, pyrin domain-containing 3 (NLRP3) inflammasome activation in J774.1, a murine macrophage cell line, and mouse primary bone marrow-derived macrophages. We showed that cyclic stretch inhibited adenosine triphosphate (ATP)-stimulated interleukin (IL)-1β secretion in lipopolysaccharide (LPS)-primed macrophages using ELISA and Western blot analyses. Cyclic stretch did not affect the degradation of the Inhibitor of κB or the nuclear translocation/transcriptional activity of nuclear factor (NF)-κB, suggesting that cyclic stretch-mediated inhibition was independent of the NF-κB signaling pathway. Consistent with these results, cyclic stretch did not affect the LPS-induced expression of inflammasome components, such as pro-IL-1β and NLRP3, which is known to require the activation of NF-κB signaling. We showed that the cyclic stretch-mediated inhibition of IL-1β secretion was caused by the suppression of caspase-1 activity. The addition of compound C, a specific inhibitor of adenosine monophosphate-activated protein kinase (AMPK), to LPS-primed macrophages inhibited IL-1β secretion as well as caspase-1 activation, suggesting that AMPK signaling is involved in ATP-triggered IL-1β secretion. Furthermore, the phosphorylation of AMPK induced by ATP in LPS-primed macrophages was significantly suppressed by cyclic stretch, indicating that cyclic stretch negatively regulates IL-1β secretion through the inhibition of caspase-1 activity by attenuating the AMPK pathway. Our results suggest that mechanical stress functions to maintain homeostasis through the prevention of excessive inflammasome activation in macrophages in mechanical microenvironments.

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Section: Discussionmentioning

confidence: 78%

Cyclic Stretch Negatively Regulates IL-1β Secretion Through the Inhibition of NLRP3 Inflammasome Activation by Attenuating the AMP Kinase Pathway

et al. 2018

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“…Regardless of how lung injury initially triggers the TLR4/ MyD88 signaling pathway that activates NF-κB, alveolar macrophages are likely to be the major cells that receive the initial pro-inflammatory signal and transduce it into cytokine signals that prolong and exacerbate injury. Stretching and inflammation are sufficient to cause these macrophages to release inflammatory cytokines (36,37), and it was shown that the ventilation-induced activation of NF-κB in alveolar macrophages induces the secretion of IL-6 and subsequent IL-1β (38). Therefore, we complemented our in vivo experiments in rats with in vitro experiments using alveolar macrophage cultures.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibody against Toll-like receptor 4 attenuates ventilator-induced lung injury in rats by inhibiting MyD88- and NF-κB-dependent signaling

Huang

Pan

Lin

et al. 2017

International Journal of Molecular Medicine

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The mechanisms through which mechanical ventilation causes non-infectious inflammatory diseases and lung injury are poorly understood. Animals models of this type of injury suggest that it involves signaling mediated by Toll‑like receptor (TLR)4 and 9. In this study, in order to gain further insight into the involvement of TLR4 in this type of injury, we performed in vivo and in vitro experiments to determine the mechanisms through which TLR4 triggers inflammation. We also examined whether the use of TLR4 monoclonal antibody (mAb) can alleviate this type of injury. For this purpose, rats were tracheotomized and administered intratracheal injections of anti‑TLR4 mAb or saline, and then ventilated for 4 h at a high tidal volume (HTV) of 40 ml/ kg or allowed to breathe spontaneously for the same period of time (controls). Alveolar macrophages (AMs) were isolated from the bronchoalveolar lavage fluid (BALF) of the rats and stimulated for 16 h with tumor necrosis factor (TNF)‑α in the presence or absence of anti‑TLR4 mAb. Lung injury was assessed by examining lung histopathology, lung wet/dry weight ratio, BALF total protein and cytokine levels in BALF and plasma. The mRNA and protein expression levels of TLR4, TLR9, myeloid differentiation factor 88 (Myd88) and nuclear factor (NF)‑κB were measured in cultured macrophages. Compared to the controls (spontaneous breathing), the ventilated rats exhibited greater pulmonary permeability, more severe inflammatory cell infiltration/lung edema, and higher levels of interleukin (IL)‑1β, IL‑6 and TNF‑α in BALF and plasma. The AMs from the ventilated rats expressed higher mRNA and protein levels of TLR4, TLR9, Myd88 and NF‑κB compared with the macrophages from the spontaneously breathing rats. The ventilated rats pre‑treated with anti‑TLR4 mAb exhibited markedly attenuated signs of ventilation‑induced injury, such as less lung inflammation and pulmonary edema, fewer cells in BALF, and lower levels of ILs and TNF‑α in BALF and plasma. Similarly, the TNF‑α‑dependent increases in the mRNA and protein expression of TLR4, Myd88 and NF‑κB in AMs were attenuated when TNF‑α was co‑administered with anti‑TLR4 mAb than when TNF-α was administered alone. Co‑administering anti-TLR4 mAb also reduced the TNF‑α‑dependent secretion of ILs. On the whole, our data demonstrate that TLR4 contributes significantly to ventilation‑induced lung injury by activating the Myd88/NF‑κB pathway, and pre‑treating rats with anti‑TLR4 mAb partially protects them against this type of injury by inhibiting Myd88/NF-κB signaling.

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“…Transition to the M2 phenotype has been associated with improved cardiac outcomes post MI (124, 212). Hypoxia has been shown to reduce the ability of macrophages to change their shape and orientation in response to mechanical stretch (148). Much more work is needed to fully understand the contributions of mechanics to the MI inflammatory response.…”

Section: Biomechanics Of Cardiac Function Post-mimentioning

confidence: 99%

Biomechanics of Cardiac Function

Voorhees

Han

2015

Comprehensive Physiology

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The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments.

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Hypoxia suppresses stretch-induced elongation and orientation of macrophages

Cited by 7 publications

References 34 publications

Cyclic Stretch Negatively Regulates IL-1β Secretion Through the Inhibition of NLRP3 Inflammasome Activation by Attenuating the AMP Kinase Pathway

Cyclic Stretch Negatively Regulates IL-1β Secretion Through the Inhibition of NLRP3 Inflammasome Activation by Attenuating the AMP Kinase Pathway

Monoclonal antibody against Toll-like receptor 4 attenuates ventilator-induced lung injury in rats by inhibiting MyD88- and NF-κB-dependent signaling

Biomechanics of Cardiac Function

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