Toll-like receptor 2 signalling: Significance in megakaryocyte development through wnt signalling cross-talk and cytokine induction

Undi, Ram Babu; Sarvothaman, Shilpa; Kovuru, Narasaiah; Gutti, Usha; Gutti, Ravi Kumar

doi:10.1016/j.cyto.2016.05.007

Cited by 23 publications

(17 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of TLR2 on megakaryocytes was studied in the megakaryocytic cell lines Meg-01 and Dami (62,63). Stimulation of Meg-01 with Pam3CSK4 trigger the activation of NF-kappaB, AKT and ERK1/2 pathways and, up-regulation of transcription factors involved in megakaryocyte maturation, accompanied by increases in megakaryocyte ploidy (index of maturation), thrombotic markers and adhesion to extracellular matrices (63).…”

Section: Tlr2 Involvement In Megakaryocytopoiesismentioning

confidence: 99%

Platelet toll-like receptors in thromboinflammation

Schattner¹

2017

Front Biosci

View full text Add to dashboard Cite

Besides their undiscussed role in hemostasis and thrombosis, platelets are also key effector cells capable of assisting and modulating inflammatory reactions and immune responses. Platelets play a sentinel role in immune surveillance by recognizing danger signals from pathogens and cell damage through the expression of toll-like receptors (TLRs) on its surface and internal compartments. Platelets express all 10 TLRs transcripts and its signalosome, including adaptor proteins and transcription factors. The activation of these receptors in platelets triggers hemostatic and inflammatory responses which participate in the host's response to bacterial and viral infections, linking thrombosis with infection and immunity. Among the responses elicited by the activation of platelet TLRs are platelet adhesion and aggregation, formation of mixed platelet-leukocyte aggregates, expression and secretion of cytokines and quemokines, and thrombin generation. TLRs also are expressed in megakaryocytes, and their activation regulates not only platelet biogenesis, but also pro-inflammatory and antiviral responses. This review will focus on work that has shown the role of platelet TLRs, mainly in thromboinflammatory responses elicited by platelets and megakaryocytes.

show abstract

Section: Tlr2 Involvement In Megakaryocytopoiesismentioning

confidence: 99%

Platelet toll-like receptors in thromboinflammation

Schattner¹

2017

Front Biosci

View full text Add to dashboard Cite

show abstract

“…The activation of cellular WINK1, ␤-catenin, and HSP60 after 24-h galectin-3 treatment suggests the possible involvement of multiple downstream signaling pathways at later stages of the process. Toll-like receptor 2-associated IL-6 secretion from megakaryocytes has been shown to be associated with Wnt ␤-catenin signaling (31), and the presence of humanized anti-HSP60 anti- …”

Section: Galectin-3-cd146 Interaction Induces Cytokine Secretionmentioning

confidence: 99%

Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

Colomb

Wang

Simpson

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.Galectin-3 is a galactoside-binding protein that is expressed by many types of human cells. Overexpression of galectin-3 commonly occurs in most types of cancer (1, 2) and is increasingly recognized to influence cancer cell-cell and cancer-microenvironment communications and contributes to cancer development, progression, and metastasis as a result of galectin-3 interaction with various galactose-terminated glycans carried on the cell surface and in the extracellular matrix (2).Earlier studies by us as well as by other groups have revealed that the concentration of circulating galectin-3 is markedly increased, up to 30-fold, in the bloodstream of cancer patients, including those with colorectal, breast, lung, bladder, pancreatic, and head and neck cancers and melanoma (2-8). Patients with metastatic disease tend to have higher concentrations of circulating galectin-3 than those with only localized tumors (3). Our recent study has revealed that increased circulating galectin-3 is an important promoter of blood-borne metastasis in a mouse model (9). This effect of galectin-3 is shown to be partly attributed to galectin-3 interaction with the oncofetal Thomsen-Friedenreich (galactose␤1,3-N-acetyl-galactosamine ␣-, TF) disaccharide expressed on the cancer-associated transmembr...

show abstract

“…Kandi et al (2015a,b) showed that the co-expression of miR-125b and miR99a contributed to the VCR resistance to CMK cells due to actively transcribed miR99a/miR-125b locus on chromosome 21q21.1. Let7b/Fzd4 axis have been implicated in regulating mitochondrial biogenesis during megakaryocyte development through wnt signaling (Undi et al, 2016a(Undi et al, , 2016b. Natural products could be explored to regulate such mechanisms to enhance the platelet production.…”

Section: Traditional Chinese Medicinementioning

confidence: 99%