Mycobacteria-induzed macrophage activation:: role of TLR2/PI3K signaling in regulation of proinflammatory gene transcription and cytoskeletal rearrangements important for the cell motility (2006)
- Authors:
- USP affiliated authors: KIPNIS, THEREZA LIBERMAN - ICB ; SILVA, WILMAR DIAS DA - ICB
- Unidade: ICB
- Assunto: IMUNOLOGIA
- Language: Inglês
- Abstract: Rationale: Mycobacteria are known as a potent activators of macrophages able to induce production of proinflammatory mediators and elicit rapid morphological changes such as cell spreading and polarization known to be important for macrophage extravasation and migration. The main transduction pathway leading to proinflammatory genes transcription is mediated by Toll-like receptors (TLR 2 and TLR4) binding and involves MyD88, IRAK, TRAF6, NIK and IKK complex, leading to NF-kB activation. Recently, we demonstrated that other kinase cascades triggered by mycobacteria, including activation of phosphatidylinositol 3-kinase (PI3K), indirectly contribute to NF-kB-dependent gene transcription through promotion of p65/RelA and p300 transcription coactivator binding. The role of PI3K activation in mycobacteria-induced cytoskeletal rearrangements has not been early elucidated. Objective: to study whether activation of PI3K by BCG mycobacteria is mediated by TLR2 and whether the same PI3Kdependent signaling pathway leads to the proinflammatory genes transcription and macrophage cytoskeletal rearrangements.Methods and Results: Viable or lysed mycobacteria, as well as purified cell wall lipoprotein p19, TLR2 agonist, induced RAW264.7 cells to extend actin-rich pseudopods which impart radial spreading within 3 h leading later to persistent cell polarization. Cell spreading coincided with chemokine production started in BCG- infected macrophagecultures within 3h postinfection. The both effects were completely abrogated in the cells pretreated with phosphatidylinositol 3- kinase, PI3K, inhibitor (LY294002). MIP-2 production, in contrast to macrophage spreading, was highly- dependent on NF-kB activation by BCG that was verified in the cells treated with NF-kB inhibitor. BCG induced rapid activation of PI3K which was recruited to the activated TLR2 receptor. TLR2- neutralizing antibody inhibited macrophage spreading and PI3K activation induced by p19. B2-integrins blockade with a corresponding antibody inhibited macrophage spreading and polarization but had no effect on pseudopodia protrusions demonstrating the down-stream position of integrin-mediated adhesion in PI3K- dependent signaling pathway leading to motility phenotype. The obtained data demonstrate that the direct effect of mycobacteria on macrophage shape might be mediated through TLR2-dependent PI3K activation. Conclusions: 1) PI3K activation in BCG-treated macrophages might be mediated through TLR2, 2) PI3K controls early macrophage cytoskeletal rearrangements independently of its role in NF-kB-dependent chemokine gene transcription but rather through activation of small GTPases and b2-integrins, 3) the obtained data do not exclude that chemokines produced by activated macrophages contribute to the cell polarization and subsequent migration in an autocrine manner.
- Imprenta:
- Source:
- Título: Abstracts
- Conference titles: Meeting of the Brazilian Society for Immunology
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ABNT
LASUNSKAIA, Elena B et al. Mycobacteria-induzed macrophage activation:: role of TLR2/PI3K signaling in regulation of proinflammatory gene transcription and cytoskeletal rearrangements important for the cell motility. 2006, Anais.. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo, 2006. . Acesso em: 02 dez. 2025. -
APA
Lasunskaia, E. B., Campos, M. N., Darieva, Z., Andrade, M. de, Kipnis, T. L., Matta, R. da, et al. (2006). Mycobacteria-induzed macrophage activation:: role of TLR2/PI3K signaling in regulation of proinflammatory gene transcription and cytoskeletal rearrangements important for the cell motility. In Abstracts. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo. -
NLM
Lasunskaia EB, Campos MN, Darieva Z, Andrade M de, Kipnis TL, Matta R da, Einicker-Lamas M, Silva WD da. Mycobacteria-induzed macrophage activation:: role of TLR2/PI3K signaling in regulation of proinflammatory gene transcription and cytoskeletal rearrangements important for the cell motility. Abstracts. 2006 ;[citado 2025 dez. 02 ] -
Vancouver
Lasunskaia EB, Campos MN, Darieva Z, Andrade M de, Kipnis TL, Matta R da, Einicker-Lamas M, Silva WD da. Mycobacteria-induzed macrophage activation:: role of TLR2/PI3K signaling in regulation of proinflammatory gene transcription and cytoskeletal rearrangements important for the cell motility. Abstracts. 2006 ;[citado 2025 dez. 02 ] - Effect of trypanosoma cruzi membrane components on the formation of the c3 convertase of the classical pathway
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