Mechanical Ventilation Augments Poly(I:C)-Induced Lung Injury via a WISP1-Integrin β3-Dependent Pathway in Mice

Jin, Shuqing; Chen, Zhixia; Ding, Xuan; Zhao, Xiang; Tong, Yao; Billiar, Timothy R.; Li, Quan

doi:10.2119/molmed.2015.00233

Cited by 19 publications

(31 citation statements)

References 28 publications

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“…In addition, we also found that pure over-distension on healthy mice lung could only raise WISP1 level, while it could not upregulate cytokine levels (the results were not shown in this paper). Reports about WISP1 mainly concentrated on WISP1/β-catenin signaling pathway [30], like our previous study about WISP1 interacting with β6 [19,31] or with β3 [32,33], which was related to alveolarcapillary permeability in VILI or ALI/ARDS.…”

Section: Discussionsupporting

confidence: 56%

WISP1 and TLR4 on Macrophages Contribute to Ventilator-Induced Lung Injury

Wang

Zhang

et al. 2020

Inflammation

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Injurious mechanical ventilation has been shown to directly affect pulmonary and systemic immune responses. How these responses propagate or attenuate remains unknown. The goal of this study was to further determine whether toll-like receptor (TLR) 4 and WNT1-inducible signaling pathway protein 1 (WISP1) could contribute to injurious mechanical ventilation, especially focusing on the role of macrophages during experimental ventilator-induced lung injury. A prospective, randomized, and controlled animal study was designed, and male, wild-type (WT) C57BL/6 mice, TLR4 knockout (TLR4 −/− ), and lyzTLR4 knockout (lyzTLR4 −/− ) mice aging 8~12 weeks were used. Animals were anesthetized and randomized to spontaneous breathing (SB) group or to high tidal volume (VT, 20 ml/kg) mechanical ventilation (HTV) group. Histological evaluation, alveolarcapillary permeability of Evan's blue albumin (EBA), WISP1 protein levels, macrophage inflammatory protein-2 (MIP-2), and interleukin-6 (IL-6) in plasma and bronchoalveolar lavage fluid (BALF) concentrations were analyzed. HTV group was associated with a significant increase of WISP1 and EBA ratio in C57BL/6 mice, a significant decrease of WISP1 protein levels, and a significant decrease of IL-6, MIP-2 in plasma, and BALF concentrations of pro-inflammatory cytokines in TLR4 −/− and lyzTLR4 −/− knockout mice. In TLR4 −/− mice and lyzTLR4 −/− mice, there were also significant differences between SB group and HTV group in terms of H&E score and EBA ratio and level of pro-inflammation cytokines. The entire TLR4-targeted mice could further improve various inflammatory changes and damages when compared with lyzTLR4-targeted mice. What is more, TLR4 −/ − mice and lyzTLR4 −/− mice reacted differently to rWISP1 and/or BMMC treated. TLR4 −/− Zhuang Yu and Tingting Wang contributed equally to this work.

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Section: Discussionsupporting

confidence: 56%

WISP1 and TLR4 on Macrophages Contribute to Ventilator-Induced Lung Injury

Wang

Zhang

et al. 2020

Inflammation

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“…In-vitro mechanical stretch of type II epithelial cells activated innate immunity and increased WISP1 expression, providing fundamental support for its involvement in VILI [ 41 ]. We noted that intrapulmonary WISP1 is elevated in VILI [ 21 ], CLP [ 22 , 23 ], combined poly(I:C) and mechanical ventilation [ 42 ], and in the current report in combined CLP and MTV; neutralizing antibodies to WISP1 partially reduced lung injury and inflammation in all of these conditions. The potential convergence of WNT/β-catenin signaling and WISP1 adds to its importance in VILI [ 43 ] as well as WNT-mediated lung epithelial cell repair [ 44 ].…”

Section: Discussionmentioning

confidence: 58%

Mechanical ventilation enhances extrapulmonary sepsis-induced lung injury: role of WISP1–αvβ5 integrin pathway in TLR4-mediated inflammation and injury

et al. 2018

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BackgroundHigh tidal volume ventilation of healthy lungs or exacerbation of existing acute lung injury (ALI) by more moderate mechanical ventilation (MTV) produces ventilator-induced lung injury. It is less clear whether extrapulmonary sepsis sensitizes the lung to MTV.MethodsWe used a two-hit model of cecal ligation and puncture (CLP) followed 12 h later by MTV (10 ml/kg; 6 h) to determine whether otherwise noninjurious MTV enhances CLP-induced ALI by contrasting wildtype and TLR4−/− mice with respect to: alveolar-capillary permeability, histopathology and intrapulmonary levels of WNT-inducible secreted protein 1 (WISP1) and integrin β5; plasma levels of cytokines and chemokines (TNF-α, IL-6, MIP-2, MCP-1) and intrapulmonary neutrophil infiltration; and other inflammatory signaling via intrapulmonary activation of JNK, p38 and ERK. A separate cohort of mice was pretreated with intratracheal neutralizing antibodies to WISP1, integrin β5 or IgG as control and the presented phenotyping repeated in a two-hit model; there were 10 mice per group in these first three experiments. Also, isolated peritoneal macrophages (PM) from wildtype and TLR4−/−, MyD88−/− and TRIF−/− mice were used to identify a WISP1–TLR4–integrin β5 pathway; and the requisite role of integrin β5 in WISP1-induced cytokine and chemokine production in LPS-primed PM was examined by siRNA treatment.ResultsMTV, that in itself did not cause ALI, exacerbated increases in alveolar-capillary permeability, histopathologic scoring and indices of pulmonary inflammation in mice that previously underwent CLP; the effects of this two-hit model were abrogated in TLR4−/− mice. Attendant with these findings was a significant increase in intrapulmonary WISP1 and integrin β5 in the two-hit model. Anti-WISP1 or anti-integrin β5 antibodies partially inhibited the two-hit phenotype. In PM, activation of TLR4 led to an increase in integrin β5 expression that was MyD88 and NF-κB dependent. Recombinant WISP1 increased LPS-induced cytokine release in PM that was inhibited by silencing either TLR4 or integrin β5.ConclusionsThese data show for the first time that otherwise noninjurious mechanical ventilation can exacerbate ALI due to extrapulmonary sepsis underscoring a potential interactive contribution of common events (sepsis and mechanical ventilation) in critical care, and that a WISP1–TLR4–integrin β5 pathway contributes to this phenomenon.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2237-0) contains supplementary material, which is available to authorized users.

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“…Although we 10 reported that WISP1-β6 complexes in lung were important in cecal ligation and puncture (CLP), the non-specificity of inhibition of integrins with RGD and the partial effect observed with neutralizing antibodies to β6 suggest that other RGD sensitive integrins may play a role. Less is known about β3 and WISP1, we recently found that WISP1-integrinβ3 interaction contributed to mechanical ventilation augmented PolyI:C induced lung injury 14 . αvβ3 integrin (vitronectin receptor, CD51/CD61) is a ubiquitous receptor that is expressed on a wide variety of cell types including differentiated macrophage 15 16 .…”

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confidence: 95%

WISP1-αvβ3 integrin signaling positively regulates TLR-triggered inflammation response in sepsis induced lung injury

Chen

Ding

Jin

et al. 2016

Sci Rep

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We recently noted that the matricellular protein WISP1 contributes to sepsis induced acute lung injury (ALI) via integrin β6. In the current study, we pursued further aspects of WISP1 modulation of TLR signaling in lungs of mice after sepsis and TLR4 mediated release of TNF-α in macrophages. After confirming that TLR4 and CD14 are critical in transducing sepsis mediated ALI, we now demonstrate that intrapulmonary αvβ3 is increased by polymicrobrial sepsis in a TLR4, CD14 dependent fashion. Comparison of cultured macrophages revealed that WISP1 increased release of TNF-α from RAW264.7 cells with baseline expression of αvβ3, but primary cultures of peritoneal macrophages (PMø) required activation of TLR4 to induce de novo synthesis of αvβ3 enabling WISP1 to stimulate release of TNF-α. The specific requirement for β3 integrin was apparent when the effect of WISP1 was lost in PMø isolated from β3−/− mice. WISP1 enhanced TLR4 mediated ERK signaling and U0126 (an ERK inhibitor) blocked LPS induced β3 integrin expression and WISP1 enhanced TNF-α release. Collectively these data suggest that WISP1-αvβ3 integrin signaling is involved in TLR4 pathways in macrophages and may be an important contributor to TLR4/CD14 mediated inflammation in sepsis induced lung injury.

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Mechanical Ventilation Augments Poly(I:C)-Induced Lung Injury via a WISP1-Integrin β3-Dependent Pathway in Mice

Cited by 19 publications

References 28 publications

WISP1 and TLR4 on Macrophages Contribute to Ventilator-Induced Lung Injury

WISP1 and TLR4 on Macrophages Contribute to Ventilator-Induced Lung Injury

Mechanical ventilation enhances extrapulmonary sepsis-induced lung injury: role of WISP1–αvβ5 integrin pathway in TLR4-mediated inflammation and injury

WISP1-αvβ3 integrin signaling positively regulates TLR-triggered inflammation response in sepsis induced lung injury

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