TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury

Ding, Xuan; Jin, Shuqing; Tong, Yao; Chen, Zhixia; Mei, Shuya; Zhang, Liming; Billiar, Timothy R.; Li, Quan

doi:10.1038/srep34278

Cited by 35 publications

(28 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TLR3 which is a nucleic acid sensing receptor involved in response to viral pathogens, but also to sterile tissue damage (reviewed by Tatematsu et al, 2014). TLR3 can be also upregulated by LPS via TLR4-dependent pathway (Ding et al, 2017). TLR4 is stimulated by bacterial LPS (Lu et al, 2008), but also during viral infections, for example by Ebola glycoproteins (Okumura et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

A Potent Anti-Inflammatory Response in Bat Macrophages May Be Linked to Extended Longevity and Viral Tolerance

Kacprzyk

Hughes

Pålsson-McDermott

et al. 2017

Acta Chiropterologica

View full text Add to dashboard Cite

Bats are unique among mammals given their ability to fly, apparent tolerance of deadly viruses and extraordinary longevity. We propose that these traits are linked and driven by adaptations of the innate immune system. To explore this hypothesis we challenged macrophages from the greater mouse-eared bat, Myotis myotis and the house mouse, Mus musculus with Toll Like Receptors (TLRs) ligands, lipopolysaccharides, LPS and polyinosinic-polycytidylic acid, Poly(I:C). Macrophages from both species presented a high level of mRNA induction of inferon β (INF-β), tumor necrosis factor (TNF) and interleukin-1β (Il-1β). However, in bat macrophages, this antiviral, proinflammatory response was balanced by a sustained high-level transcription of the anti-inflammatory cytokine Il-10, which was not observed in mouse, potentially resulting from adaptive regulation in bats.Additionally, phylogenomic selection tests across the basal divergences in mammals (n = 39) uncovered bat-specific adaptations in six genes involved in antiviral and proinflammatory signalling. Based on this pilot study, we put forward a hypothesis that bats may have evolved unique anti-inflammatory responses to neutralize proinflammatory stimuli resulting from flight. This in turn may drive their extraordinary longevity and viral tolerance by limiting inflammation driven ageing and infection-induced immunopathology. Further data from other individuals and bat species are required to advance this intriguing hypothesis.

show abstract

Section: Discussionmentioning

confidence: 99%

A Potent Anti-Inflammatory Response in Bat Macrophages May Be Linked to Extended Longevity and Viral Tolerance

Kacprzyk

Hughes

Pålsson-McDermott

et al. 2017

Acta Chiropterologica

View full text Add to dashboard Cite

show abstract

“…5,12,17,19 There is also crosstalk between TLR4 and TLR3. 26 Due to the crosstalk, different ligands can utilize components of TLR-dependent pathways to various degrees. 19 TLR4-MyD88-NF-κB signaling seems to influence TLR3 function, which explains the synergistic effect between TLR4 and TLR3 triggering in macrophages that has been observed in acute lung injury.…”

Section: General Consequences Of Tlr4 Stimulationmentioning

confidence: 99%

“…19 TLR4-MyD88-NF-κB signaling seems to influence TLR3 function, which explains the synergistic effect between TLR4 and TLR3 triggering in macrophages that has been observed in acute lung injury. 26 As a result of TLR4 stimulation of the dependent biochemical cascades, the generation of various short-chain RNA molecules (miRNA) becomes activated. For example, miRNA-511 positively regulates TLR4 signaling, but miRNA-200c silences MyD88 and impairs the LPS-induced expression of pro-inflammatory cytokines like IL-6, CXCL9 and TNF-α.…”

Section: General Consequences Of Tlr4 Stimulationmentioning

confidence: 99%

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Zmonarski¹,

Banasik²,

Madziarska³

et al. 2019

Adv Clin Exp Med

View full text Add to dashboard Cite

Krajewska M. The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells. AbstractThe innate immune system is activated before an adaptive immune response. An expression of a particular toll-like receptor (TLR) in a transplanted kidney depends on the localization of specific cells (e.g., endothelium, elements of the nephron structure), recent pathology and the time passed since transplantation. The TLR4 receptor is expressed on renal tubular epithelial (RTE) and endothelial cells, podocytes, blood and interstitial monocytes/macrophages, and dendritic cells. While circulating in blood, some monocytes are attracted and penetrate the transplanted organ, where they supplement the donor's resident macrophages. The intensity of migration depends on the local activation of inflammation in the graft and on the expression of specific receptors on kidney endothelial cells and monocytes/macrophages. The percentage of cells with shifted TLR4 expression usually increases in circulating monocytes. The TLR4 and the biochemical stimulation cascade derived from it in any type of cell, including monocytes, undergo multi-level regulation with feedback loops with other components of the primary system, and are also dependent on the action of immunosuppression. Toll-like receptor 4 senses stimuli that make monocytes contribute differently both to acute/chronic kidney injuries and to the development of tolerance. After kidney transplantation, TLR4 expression and related cytokine production capacity may vary depending on past diseases and oncoming problems. Since conventional immunosuppression does not prevent chronic allograft injury (CAI), peripheral blood monocytes and TLR4 constitute candidates for diagnostic and therapeutic targets. Considering the mutual communication among various elements of the primary immune system, future therapeutic intervention should be directed toward factors directly or indirectly regulating the expression or post-receptor signaling of the TLR4 receptor.

show abstract

“…It has been reported previously that synergy between viral and bacterial TLR signaling could lead to amplification of the inflammatory response [11,12,21]. Mechanical ventilation, which is a component of supportive therapy in the management of acute lung injury, can also produce an iatrogenic complication referred to as ventilator-induced lung injury (VILI).…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2020

Inflammation

Self Cite

View full text Add to dashboard Cite

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.

show abstract

TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury

Cited by 35 publications

References 59 publications

A Potent Anti-Inflammatory Response in Bat Macrophages May Be Linked to Extended Longevity and Viral Tolerance

A Potent Anti-Inflammatory Response in Bat Macrophages May Be Linked to Extended Longevity and Viral Tolerance

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

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

Contact Info

Product

Resources

About