Targeted deletion of the tachykinin 4 gene (TAC4−/−) influences the early stages of B lymphocyte development

Berger, Alexandra; Benveniste, Patricia; Corfe, Steven A.; Tran, Anne H.; Barbara, Mary; Wakeham, Andrew; Mak, Tak W.; Iscove, Norman N.; Paige, Christopher J.

doi:10.1182/blood-2010-06-291062

Cited by 21 publications

(22 citation statements)

References 33 publications

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“…Additionally, tachykinins and their interaction with their receptors seem to be important in the neoplastic transformation of bone marrow, leading to the development of acute leukaemia and other haematological cancers [93, 96, 97]. HK-1 is known to have a crucial role in the regulation of bone marrow microenvironment, both physiologic and towards malignant transformation [98].…”

Section: Tumor Microenvironment and The Nk-1 Receptormentioning

confidence: 99%

“…TAC4 encodes for the HK-1 receptor. These findings suggest an inhibitory role for HK-1 on developing B cells, and that it is part of the bone marrow microenvironment that supports and regulates the proliferation and differentiation of hematopoietic cells [96]. In another study, the presence of SP in B lymphocytes of hypoplastic bone marrow predicted neoplastic transformation [97].…”

Section: Tumor Microenvironment and The Nk-1 Receptormentioning

confidence: 99%

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The Role of Neurokinin-1 Receptor in the Microenvironment of Inflammation and Cancer

Rosso

Muñoz

Berger

2012

The Scientific World Journal

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The recent years have witnessed an exponential increase in cancer research, leading to a considerable investment in the field. However, with few exceptions, this effort has not yet translated into a better overall prognosis for patients with cancer, and the search for new drug targets continues. After binding to the specific neurokinin-1 (NK-1) receptor, the peptide substance P (SP), which is widely distributed in both the central and peripheral nervous systems, triggers a wide variety of functions. Antagonists against the NK-1 receptor are safe clinical drugs that are known to have anti-inflammatory, analgesic, anxiolytic, antidepressant, and antiemetic effects. Recently, it has become apparent that SP can induce tumor cell proliferation, angiogenesis, and migration via the NK-1 receptor, and that the SP/NK-1 receptor complex is an integral part of the microenvironment of inflammation and cancer. Therefore, the use of NK-1 receptor antagonists as a novel and promising approach for treating patients with cancer is currently under intense investigation. In this paper, we evaluate the recent scientific developments regarding this receptor system, its role in the microenvironment of inflammation and cancer, and its potentials and pitfalls for the usage as part of modern anticancer strategies.

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Section: Tumor Microenvironment and The Nk-1 Receptormentioning

confidence: 99%

Section: Tumor Microenvironment and The Nk-1 Receptormentioning

confidence: 99%

The Role of Neurokinin-1 Receptor in the Microenvironment of Inflammation and Cancer

Rosso

Muñoz

Berger

2012

The Scientific World Journal

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“…In humans, the expression of hHK-1 and NK1R, but not SP, was similarly detected in B cells, and in contrast to SP, hHK-1 was able to induce human pre-B-cells proliferation through an NK1R-independent mechanism (94). By contrast, the knockout of Tac4 (Tac4 -/-) increased the pro-B-cell population twofold in mouse bone marrow in vivo and in in vitro culture (95). HK-1 application to cell cultures of long-term reconstituting stem cells led to a more than 80% decrease in de novo generated pro-B cells (in terms of absolute cell number), without inducing cell death.…”

Section: Tks and Hematopoiesismentioning

confidence: 99%

Tachykinin: recent developments and novel roles in health and disease

Onaga

2014

Biomolecular Concepts

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Over 80 years has passed since the discovery of substance P (SP), and a variety of peptides of the tachykinin (TK) family have been found and investigated. SP, neurokinin A (NKA), and neurokinin B (NKB) are representative peptides in mammalian species. SP and NKA are major excitatory neurotransmitters in the peripheral nervous system, while NKB is primarily involved in the central nervous system (CNS). Moreover, TK peptides play roles not only as neurotransmitters but also as local factors and are involved in almost all aspects of the regulation of physiological functions and pathophysiological processes. The role of SP as a mediator of pain processing and inflammation in peripheral tissues in coordination with transient receptor potential channels is well established, while novel aspects of TKs in relation to hematopoiesis, venous thromboembolism, tendinopathy, and taste perception have been clarified. In the CNS, the NKB signaling system in the hypothalamus has been shown to play a crucial role in the regulation of gonadotropin hormone secretion and the onset of puberty, and molecular biological studies have elucidated novel prophylaxic activities of TKs against neurogenic movement disorders based on their molecular structure. This review provides an overview of the novel aspects of TKs reported around the world in the last 5 years, with particular focus on nociception, inflammation, hemopoiesis, gonadotropin secretion, and CNS diseases.

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“…TAC4 is expressed in a variety of peripheral immune cells, including lymphocytes, monocytes and macrophages [8]–[10]. Accordingly, HK-1 is involved in immune functions and inflammation [2], [5], [11]–[14]. However, its role in the nervous system remains almost unknown.…”

Section: Introductionmentioning

confidence: 99%

Hemokinin-1 Gene Expression Is Upregulated in Microglia Activated by Lipopolysaccharide through NF-κB and p38 MAPK Signaling Pathways

et al. 2012

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The mammalian tachykinins, substance P (SP) and hemokinin-1 (HK-1), are widely distributed throughout the nervous system and/or peripheral organs, and function as neurotransmitters or chemical modulators by activating their cognate receptor NK1. The TAC1 gene encoding SP is highly expressed in the nervous system, while the TAC4 gene encoding HK-1 is uniformly expressed throughout the body, including a variety of peripheral immune cells. Since TAC4 mRNA is also expressed in microglia, the resident immune cells in the central nervous system, HK-1 may be involved in the inflammatory processes mediated by these cells. In the present study, we found that TAC4, rather than TAC1, was the predominant tachykinin gene expressed in primary cultured microglia. TAC4 mRNA expression was upregulated in the microglia upon their activation by lipopolysaccharide, a well-characterized Toll-like receptor 4 agonist, while TAC1 mRNA expression was downregulated. Furthermore, both nuclear factor-κB and p38 mitogen-activated protein kinase intracellular signaling pathways were required for the upregulation of TAC4 mRNA expression, but not for the downregulation of TAC1 mRNA expression. These findings suggest that HK-1, rather than SP, plays dominant roles in the pathological conditions associated with microglial activation, such as neurodegenerative and neuroinflammatory disorders.

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Targeted deletion of the tachykinin 4 gene (TAC4−/−) influences the early stages of B lymphocyte development

Cited by 21 publications

References 33 publications

The Role of Neurokinin-1 Receptor in the Microenvironment of Inflammation and Cancer

The Role of Neurokinin-1 Receptor in the Microenvironment of Inflammation and Cancer

Tachykinin: recent developments and novel roles in health and disease

Hemokinin-1 Gene Expression Is Upregulated in Microglia Activated by Lipopolysaccharide through NF-κB and p38 MAPK Signaling Pathways

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