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Maa MC, Leu TH. Src is required for migration, phagocytosis, and interferon beta production in Toll-like receptor-engaged macrophages. Biomedicine (Taipei). 2016;6(3):14doi: 10.7603/s40681-016-0014-4.
Maa, M. C., & Leu, T. H. (2016). Src is required for migration, phagocytosis, and interferon beta production in Toll-like receptor-engaged macrophages. BioMedicine, 6(3), 14. https://doi.org/10.7603/s40681-016-0014-4
Maa, Ming-Chei, and Leu, Tzeng-Horng. "Src is required for migration, phagocytosis, and interferon beta production in Toll-like receptor-engaged macrophages." BioMedicine vol. 6,3 (2016): 14. doi: https://doi.org/10.7603/s40681-016-0014-4
Maa MC, Leu TH. Src is required for migration, phagocytosis, and interferon beta production in Toll-like receptor-engaged macrophages. Biomedicine (Taipei). 2016 Jun;6(3):14. doi: 10.7603/s40681-016-0014-4. Epub 2016 Aug 12. PMID: 27514533; PMCID: PMC4980824.
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Biomedicine (Taipei). 2016 Jun;6(3):14. doi: 10.7603/s40681-016-0014-4. Epub 2016 Aug 12.

Src is required for migration, phagocytosis, and interferon beta production in Toll-like receptor-engaged macrophages.

BioMedicine

Ming-Chei Maa, Tzeng-Horng Leu

Affiliations

  1. Graduate Institute of Basic Medical Science, China Medical University, 404, Taichung, Taiwan. [email protected].
  2. Institute of Basic Medical Sciences, China Medical University, 404, Taichung, Taiwan.
  3. Department of Pharmacology, China Medical University, 404, Taichung, Taiwan.
  4. Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, 701, Tainan, Taiwan.
  5. Department of Pharmacology, College of Medicine, National Cheng Kung University, 701, Tainan, Taiwan.

PMID: 27514533 PMCID: PMC4980824 DOI: 10.7603/s40681-016-0014-4

Abstract

As an evolutionarily conserved mechanism, innate immunity controls self-nonself discrimination to protect a host from invasive pathogens. Macrophages are major participants of the innate immune system. Through the activation of diverse Toll-like receptors (TLRs), macrophages are triggered to initiate a variety of functions including locomotion, phagocytosis, and secretion of cytokines that requires the participation of tyrosine kinases. Fgr, Hck, and Lyn are myeloid-specific Src family kinases. Despite their constitutively high expression in macrophages, their absence does not impair LPS responsiveness. In contrast, Src, a barely detectable tyrosine kinase in resting macrophages, becomes greatly inducible in response to TLR engagement, implicating its role in macrophage activation. Indeed, silencing Src suppresses the activated TLR-mediated migration, phagocytosis, and interferon-beta (IFN-β) secretion in macrophages. And these physiological defects can be restored by the introduction of siRNA-resistant Src. Notably, the elevated expression and activity of Src is inducible nitric oxide synthase (iNOS)-dependent. Due to (1) iNOS being a NF-κB target, which can be induced by various TLR ligands, (2) Src can mediate NF-κB activation, therefore, there ought to exist a loop of signal amplification that regulates macrophage physiology in response to the engagement of TLRs.

Keywords: IFN-β; Macrophage activation; Src; Toll-like receptors

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