Journal ArticleDOI
Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.
Laurence Arbibe,Jean Paul Mira,Jean Paul Mira,Nicole Teusch,Lois Kline,Mausumee Guha,Nigel Mackman,Paul J. Godowski,Richard J. Ulevitch,Ulla G. Knaus +9 more
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TLDR
TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2, and Rac1 controls a second, IκB–independent, pathway to NF-κB activation and is essential in innate immune cell signaling via TLR 2.Abstract:
Mammalian Toll-like receptors (TLRs) are expressed on innate immune cells and respond to the membrane components of Gram-positive or Gram-negative bacteria. When activated, they convey signals to transcription factors that orchestrate the inflammatory response. However, the intracellular signaling events following TLR activation are largely unknown. Here we show that TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2. Dominant-negative Rac1N17, but not dominant-negative Cdc42N17, block nuclear factor-κB (NF-κB) transactivation. S. aureus stimulation causes the recruitment of active Rac1 and phosphatidylinositol-3 kinase (PI3K) to the TLR2 cytosolic domain. Tyrosine phosphorylation of TLR2 is required for assembly of a multiprotein complex that is necessary for subsequent NF-κB transcriptional activity. A signaling cascade composed of Rac1, PI3K and Akt targets nuclear p65 transactivation independently of IκBα degradation. Thus Rac1 controls a second, IκB–independent, pathway to NF-κB activation and is essential in innate immune cell signaling via TLR2.read more
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Differential effects of the Toll-like receptor 2 agonists, PGN and Pam3CSK4 on anti-IgE induced human mast cell activation.
TL;DR: The differential modulations of anti-IgE induced mast cell activation by PGN and Pam3CSK4 suggest that dimerization of TLR2 with TLR1 or TLR6 produced different modulating actions on FcεRI mediated human mast cellactivation.
Journal ArticleDOI
SCIMP is a universal Toll-like receptor adaptor in macrophages.
Lin Luo,James E. B. Curson,Liping Liu,Adam A. Wall,Neeraj Tuladhar,Richard Lucas,Matthew J. Sweet,Jennifer L. Stow +7 more
TL;DR: It is reported here that SCIMP is phosphorylated and activated in response to agonists of multiple TLRs, including TLR2,TLR3, TLR4, and TLR9, and is thus a universal TLR adaptor for scaffolding the Lyn tyrosine kinase and its effectors to enable responses against a wide range of danger signals.
Journal ArticleDOI
Toll-like receptor 2 mediates vascular contraction and activates RhoA signaling in vascular smooth muscle cells from STZ-induced type 1 diabetic rats.
TL;DR: It is demonstrated that aortas from STZ-diabetic rats exhibit increased expression of TLR2 and its adaptor protein, myeloid differentiation primary response 88 (MyD88), as well as enhanced protein–protein interaction between TLR 2 and MyD88, suggesting a TLR1 signaling activation.
Journal ArticleDOI
CD11b regulates antibody class switching via induction of AID.
Seohyun Park,Hyunsub Sim,Hye-In Kim,Daecheol Jeong,Guang Wu,Soo Young Cho,Young Seek Lee,Hyung-Joo Kwon,Keunwook Lee +8 more
TL;DR: The induction of CD11b in activated B2 B cells is reported and its unexpected role in immunoglobulin heavy chain class switch recombination (CSR) is defined and emphasized, with experimental evidence emphasized the function of CD 11b in antibody responses and the role ofCD11b as a vital regulator of CSR.
Journal ArticleDOI
Macrophage-Mediated Inflammation in Skin Wound Healing
Alireza Hassanshahi,Mohammad Moradzad,Saman Ghalamkari,Moosa Fadaei,Allison J. Cowin,Mohammadhossein Hassanshahi +5 more
TL;DR: Different cellular and molecular aspects of macrophage-mediated skin wound healing are discussed, alongside important aspects such as Macrophage subtypes, metabolism, plasticity, and epigenetics.
References
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Journal ArticleDOI
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
TL;DR: The cloning and characterization of a human homologue of the Drosophila toll protein (Toll) is reported, which has been shown to induce the innate immune response in adult Dosophila.
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Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components.
Osamu Takeuchi,Katsuaki Hoshino,Taro Kawai,Hideki Sanjo,Haruhiko Takada,Tomohiko Ogawa,Kiyoshi Takeda,Shizuo Akira +7 more
TL;DR: It is demonstrated that TLR2 and TLR4 recognize different bacterial cell wall components in vivo andTLR2 plays a major role in Gram-positive bacterial recognition.
Journal ArticleDOI
Toll-like receptors in the induction of the innate immune response
Alan Aderem,Richard J. Ulevitch +1 more
TL;DR: A group of proteins that comprise the Toll or Toll-like family of receptors perform this role in vertebrate and invertebrate organisms and it is therefore not surprising that studies of the mechanism by which they act has revealed new and important insights into host defence.
Journal ArticleDOI
Rho GTPases and signaling networks
TL;DR: The Rho GTPases form a subgroup of the Ras superfamily of 20- to 30-kD GTP-binding proteins that have been shown to regulate a wide spectrum of cellular functions, and some of the more recent exciting findings hinting at novel, unanticipated functions of the RhoGTPases are summarized.
Journal ArticleDOI
NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase
Osman N. Ozes,Lindsey D. Mayo,Jason A. Gustin,Susan R. Pfeffer,Lawrence M. Pfeffer,David B. Donner +5 more
TL;DR: It is shown that the Akt serine–threonine kinase is involved in the activation of NF-κB by tumour necrosis factor (TNF), and that Akt is part of a signalling pathway that is necessary for inducing key immune and inflammatory responses.