TLR4 Deters Perfusion Recovery and Upregulates Toll-like Receptor 2 (TLR2) in Ischemic Skeletal Muscle and Endothelial Cells

Xu, Jia; Benabou, Kelly; Cui, Xianwei; Madia, Marissa; Tzeng, Edith; Billiar, Timothy R.; Watkins, Simon C.; Sachdev, Ulka

doi:10.2119/molmed.2014.00260

Cited by 29 publications

(24 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result suggested a preferable role of TLR2 in mSC induced SC proliferation. This result was compatible with the previous reports, which revealed a signi cant role of TLR2 during muscle regeneration, because TLR2 signal could be upregulated by lipopolysaccharides and this upregulation was considered critical for muscle regeneration as this process is important for SC proliferation [39,40]. Notably, the biphasic effect of mSC on SCs resembled the role of TLR2 signaling pathway, which could be dependent on the property of in ammatory condition that triggered the muscle regeneration, such as acute or chronic muscle injury.…”

Section: Discussionsupporting

confidence: 93%

Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation

Lin

Hou

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damagebut also strengthen themuscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin(mSC) on satellite cells (SCs), which are known as the muscle stem cells. Methods: The myogenic cells, included SCs (Pax7 +) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridineassessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors. Results: Our results revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here. Conclusion: Micronized sacchachitinextracted fromGT was capable of promoting the proliferation of SC under a correct concentration.

show abstract

Section: Discussionsupporting

confidence: 93%

Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation

Lin

Hou

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In the case of the toll receptor family, for example, it was shown that extensive cross-talk between Tlr4 and Tlr2 is required in mediating adaptive responses to hind limb ischemia, when tested in non-diabetic mice. 59, 60 The present work adds RAGE to the cadre of genes that exhibit tissue microenvironment-dependent roles in inflammation and tissue regeneration. In this context, a burgeoning body of evidence links RAGE to opposing outcomes in murine models of infection challenge.…”

Section: Discussionmentioning

confidence: 98%

Ager Deletion Enhances Ischemic Muscle Inflammation, Angiogenesis, and Blood Flow Recovery in Diabetic Mice

López‐Díez

Shen

Daffu

et al. 2017

ATVB

View full text Add to dashboard Cite

Objective Diabetic subjects are at higher risk of ischemic peripheral vascular disease (PVD). We tested the hypothesis that advanced glycation end products (AGEs) and their receptor (RAGE) block neoangiogenesis and blood flow recovery after hind limb ischemia induced by femoral artery ligation (FAL) through modulation of immune/inflammatory mechanisms. Approach and Results Wild type (WT) mice rendered diabetic with streptozotocin and subjected to unilateral FAL displayed increased accumulation and expression of AGEs and RAGE in ischemic muscle. In diabetic WT mice, FAL attenuated neoangiogenesis and impaired blood flow recovery, in parallel with reduced macrophage content in ischemic muscle and suppression of early inflammatory gene expression, including chemokine (C-C motif) ligand 2 (Ccl2) and early growth response gene 1 (Egr1) versus non-diabetic mice. Deletion of Ager or transgenic expression of Glo1 (reduces AGEs) restored adaptive inflammation, neoangiogenesis and blood flow recovery in diabetic mice. In diabetes, deletion of Ager increased circulating Ly6Chi monocytes and augmented macrophage infiltration into ischemic muscle tissue after FAL. In vitro, macrophages grown in high glucose display inflammation that is skewed to expression of tissue damage versus tissue repair gene expression. Further, macrophages grown in high versus low glucose demonstrate blunted macrophage-endothelial cell interactions. In both settings, these adverse effects of high glucose were reversed by Ager deletion in macrophages. Conclusions These findings indicate that RAGE attenuates adaptive inflammation in hind limb ischemia; underscore microenvironment-specific functions for RAGE in inflammation in tissue repair versus damage; and illustrate that AGE/RAGE antagonism may fill a critical gap in diabetic PVD.

show abstract

“…Furthermore, TLR2 is only one of several TLR that utilize the myddosome as a dominant post receptor signaling mechanism (33). Another explanation for the overlapping roles for TLR2 and TLR4, and perhaps even for the more prominent role of TLR2 at the later time point, is that TLR2 can be upregulated in ischemic stress through a TLR4-dependent mechanism (35). …”

Section: Discussionmentioning

confidence: 99%

Tlr2 on Bone Marrow and Non-Bone Marrow Derived Cells Regulates Inflammation and Organ Injury in Cooperation with Tlr4 During Resuscitated Hemorrhagic Shock

Korff

Loughran

Cai

et al. 2016

Shock

View full text Add to dashboard Cite

Background Although the role of TLR4 in driving inflammation and organ injury after hemorrhagic shock and resuscitation (H/R) is well established, the role of TLR2 - another receptor for damage-associated molecular pattern (DAMP) molecules - is not. In this study, we used a combination of TLR2−/− and wild type (WT) mice treated with anti-TLR2 and anti-TLR4 neutralizing monoclonal antibodies (mAb) to discern the contribution of TLR2 relative to TLR4 to the systemic inflammatory response in murine H/R. Material and Methods WT mice, TLR2−/− and WT mice receiving an anti-TLR2 or an anti-TLR4 mAB (given as a pre-treatment) were sacrificed at 6 or 20 hr post-H/R. Bone marrow TLR2/WT chimeric mice were created to assess the importance of immune and non-immune cell-associated TLR2. Results TLR2−/− mice subjected to H/R exhibited significantly less liver damage and lower markers of systemic inflammation only at 20 hr. Bone marrow chimeric mice using combinations of TLR2−/− mice and WT mice demonstrated that TLR2 on non-bone marrow derived cells played a dominant role in the differences at 20 hr. Interestingly, WT mice treated with anti-TLR2 mAB demonstrated a reduction in organ damage and systemic inflammation at both 6 and 20 hrs following H/R. A combination of anti-TLR2 mAB and anti-TLR4 mAB showed that both receptors drive IP-10 and KC levels and that there is cooperation for increases in IL-6, MIG, and MCP-1 levels between TLR2 and TLR4. Conclusion These data also support the conclusion that TLR2 and TLR4 act in concert as important receptors in the host immune response to H/R.

show abstract

TLR4 Deters Perfusion Recovery and Upregulates Toll-like Receptor 2 (TLR2) in Ischemic Skeletal Muscle and Endothelial Cells

Abstract: Cite this article as: Xu J, et al. (2015) TLR4 deters perfusion recovery and upregulates toll-like receptor 2 (TLR2) in ischemic skeletal muscle and endothelial cells. Mol.

Cited by 29 publications

References 41 publications

Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation

Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation

Ager Deletion Enhances Ischemic Muscle Inflammation, Angiogenesis, and Blood Flow Recovery in Diabetic Mice

Tlr2 on Bone Marrow and Non-Bone Marrow Derived Cells Regulates Inflammation and Organ Injury in Cooperation with Tlr4 During Resuscitated Hemorrhagic Shock

Contact Info

Product

Resources

About