title: Toll-like receptor 2 signalling: Significance in megakaryocyte development through wnt signalling cross-talk and cytokine induction.
abstract: TLR2 is a toll-like receptor protein which is involved in innate immune responses. TLR2 recognize several virus, fungal and bacterial pathogens, upon their uptake cause internalization and cellular activation. During this process several cytokines participate including interleukins, IL6 and IL12. Interestingly, TLR2 is expressed on megakaryocytes (MKs) and platelets, which is crucial for immune mediated platelet activation. The role of TLR2 on MKs is not completely understood. We observed TLR2 induction leads to MK maturation and is involved in production of ROS which is essential for MK development. In Dami cells, TLR2 up-regulation causes increase in the cytokine production, particularly IL-6, which has been shown to stimulate CFU formation and CD41 expression. Additionally, TLR2 ligand induces wnt β-catenin signalling pathway components suggesting a cross talk between wnt and TLR pathway leading to maturation of MKs. This study shows TLR2 signalling induce cytokine production and regulate wnt signalling thereby cause maturation of MKs.
authors.affiliation: Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, Telangana, India.
authors.forename: Ram Babu
authors.initials: RB
authors.lastname: Undi
authors.affiliation: Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, Telangana, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sarvothaman
authors.affiliation: Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, Telangana, India.
authors.forename: Kovuru
authors.initials: K
authors.lastname: Narasaiah
authors.affiliation: Department of Biotechnology, GITAM Institute of Science, GITAM University, Visakhapatnam 530 045, Andhra Pradesh, India.
authors.forename: Usha
authors.initials: U
authors.lastname: Gutti
authors.affiliation: Stem Cells and Haematological Disorders Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, (PO) Gachibowli, Hyderabad 500046, Telangana, India. Electronic address: guttiravi@gmail.com.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Gutti
mesh_terms: D002460:Cell Line; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D017382:Reactive Oxygen Species; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D018664:Interleukin-12
keywords: FZD4; IL-6; Megakaryocyte; TLR2; Wnt/β-catenin