Cross Talk between MyD88 and Focal Adhesion Kinase Pathways

Zeisel, Mirjam B.; Druet, Vanessa A.; Sibilia, Jean; Klein, Jean‐Paul; Quesniaux, Valérie; Wachsmann, Dominique

doi:10.4049/jimmunol.174.11.7393

Cited by 65 publications

(57 citation statements)

References 24 publications

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“…These findings raise the intriguing possibility that the interaction between TLR4 and FAK may also regulate these cellular process and thereby serve as an important branch point in the signaling events that lead to the development of NEC. In support of this possibility, Zeisel et al (77) have reported a functional interaction between FAK and MyD88 pathways. The current findings provide additional in vivo relevance to these observations.…”

Section: Discussionmentioning

confidence: 75%

A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair

Leaphart

Cavallo

Gribar

et al. 2007

The Journal of Immunology

426

507

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Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in preterm infants and is characterized by translocation of LPS across the inflamed intestine. We hypothesized that the LPS receptor (TLR4) plays a critical role in NEC development, and we sought to determine the mechanisms involved. We now demonstrate that NEC in mice and humans is associated with increased expression of TLR4 in the intestinal mucosa and that physiological stressors associated with NEC development, namely, exposure to LPS and hypoxia, sensitize the murine intestinal epithelium to LPS through up-regulation of TLR4. In support of a critical role for TLR4 in NEC development, TLR4-mutant C3H/HeJ mice were protected from the development of NEC compared with wild-type C3H/HeOUJ littermates. TLR4 activation in vitro led to increased enterocyte apoptosis and reduced enterocyte migration and proliferation, suggesting a role for TLR4 in intestinal repair. In support of this possibility, increased NEC severity in C3H/HeOUJ mice resulted from increased enterocyte apoptosis and reduced enterocyte restitution and proliferation after mucosal injury compared with mutant mice. TLR4 signaling also led to increased serine phosphorylation of intestinal focal adhesion kinase (FAK). Remarkably, TLR4 coimmunoprecipitated with FAK, and small interfering RNA-mediated FAK inhibition restored enterocyte migration after TLR4 activation, demonstrating that the FAK-TLR4 association regulates intestinal healing. These findings demonstrate a critical role for TLR4 in the development of NEC through effects on enterocyte injury and repair, identify a novel TLR4-FAK association in regulating enterocyte migration, and suggest TLR4/FAK as a therapeutic target in this disease.

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Section: Discussionmentioning

confidence: 75%

A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair

Leaphart

Cavallo

Gribar

et al. 2007

The Journal of Immunology

426

507

View full text Add to dashboard Cite

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“…Previous studies showed that IL-6 and IL-8 release by protein I/II-activated FLS requires crosstalk between myeloid differentiation factor 88 and focal adhesion kinase, which contributes to the TLR and integrin signaling pathways, respectively (19). It is, however, conceivable that protein I/II signaling involved in BAFF synthesis might use distinct downstream signaling molecules belonging to the ␣5␤1 integrin pathway.…”

Section: Discussionmentioning

confidence: 99%

“…A large number of PRRs, such as Toll-like receptor 2 (TLR-2), TLR-4, and TLR-9, as well as numerous integrins are expressed by FLS, and their expression is increased in response to inflammatory stimuli (16,17). We previously showed that LPS, bacterial lipopeptide (BLP), and protein I/II, which are ligands of TLR-4, TLR-2, and ␣5␤1 integrin, respectively, can trigger the release of IL-6 and IL-8 from activated FLS (18,19).…”

mentioning

confidence: 99%

BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands

Alsaleh¹,

Messer²,

Semaan³

et al. 2007

Arthritis & Rheumatism

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“…Indeed, impairment of IL-1R or IL-1 plus IL-18 cleavage by ICE does not prevent bronchoconstriction or neutrophil recruitment in the airways. However, we cannot exclude that other MyD88-dependent pathways such as the recently described involvement of MyD88 in cross-talk with the focal adhesion kinase (45) or other members of the IL-1R family may be involved (46).…”

Section: Discussionmentioning

confidence: 99%

Both Hemopoietic and Resident Cells Are Required for MyD88-Dependent Pulmonary Inflammatory Response to Inhaled Endotoxin

Noulin

Quesniaux

Schnyder‐Candrian

et al. 2005

The Journal of Immunology

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Inhaled endotoxin induces an inflammatory response that contributes to the development and severity of asthma and other forms of airway disease. Here, we show that inhaled endotoxin-induced acute bronchoconstriction, TNF, IL-12p40, and KC production, protein leak, and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecule MyD88. Bronchoconstriction, inflammation, and protein leak are normal in Toll/IL-1R domain-containing adaptor inducing IFN-β-deficient mice. MyD88 is involved in TLR, but also in IL-1R-associated kinase 1-mediated IL-1R and -18R signaling. We exclude a role for IL-1 and IL-18 pathways in this response, as IL-1R1 and caspase-1 (ICE)-deficient mice develop lung inflammation while TLR4-deficient mice are unresponsive to inhaled LPS. Significantly, using bone marrow chimera, we demonstrate that both hemopoietic and resident cells are necessary for a full MyD88-dependent response to inhaled endotoxin; bronchoconstriction depends on resident cells while cytokine secretion is mediated by hemopoietic cells.

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Cross Talk between MyD88 and Focal Adhesion Kinase Pathways

Cited by 65 publications

References 24 publications

A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair

A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair

BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands

Both Hemopoietic and Resident Cells Are Required for MyD88-Dependent Pulmonary Inflammatory Response to Inhaled Endotoxin

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