Interleukin‐1β upregulates functional expression of neurokinin‐1 receptor (NK‐1R) via NF‐κB in astrocytes

Guo, Changjiang; Douglas, Steven D.; Gao, Zhiyong; Wolf, Bryan A.; Grinspan, Judith B.; Lai, Jianping; Riedel, Eric; Ho, Wen‐Zhe

doi:10.1002/glia.20079

Cited by 59 publications

(42 citation statements)

References 50 publications

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“…The increased transcription of PPT-A probably contributed to the increased expression of SP. These observations were in agreement with the results for other models, which also highlighted the involvement of NF-B activation in the increased expression of PPT-A and NK1R (Guo et al, 2004;Reed et al, 2005;Corcoran and Rameshwar, 2007).…”

Section: Discussionsupporting

confidence: 92%

Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells

Koh

Tamizhselvi²,

Bhatia³

2009

J Pharmacol Exp Ther

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The neuropeptide substance P (SP) has emerged to be an important proinflammatory mediator in acute pancreatitis (AP). The presence of substance P and its receptor, neurokinin-1 receptor (NK1R) has been shown in the pancreas and the pancreatic acinar cells. In this study, we investigated the unexplored mechanisms that mediate SP and NK1R expression using an in vitro AP model. Pancreatic acinar cells were obtained from pancreas of male Swiss mice. Isolated cells were treated with caerulein to mimic secretagogue pancreatitis. A concentration-dependent study that subjected the cells to 60 min of stimulation by caerulein showed that SP and the transcript from its gene preprotachykinin-A (PPT-A), and NK1R were up-regulated at a supraphysiological concentration of 10 Ϫ7 M. A concentration-dependent study on intracellular kinases, extracellular signal-regulated kinase (ERK1/2), and cJun N-terminal kinase (JNK) and also transcription factors nuclear factor-B (NF-B) and activator protein-1 (AP-1) showed that they were activated when the caerulein concentration was 10 Ϫ7 M. Inhibition of JNK reversed the up-regulation of PPT-A, SP, and NK1R. However, inhibition of ERK1/2 reversed the up-regulation of NK1R but not of PPT-A and SP. Furthermore, we found that specific ERK1/2 and JNK inhibitors reduce NF-B and AP-1 activity. Taken together, our results suggest that supraphysiological concentrations of caerulein up-regulate the expression of SP and NK1R in pancreatic acinar cells, and the signaling molecules that are involved in this up-regulation include ERK1/2, JNK, NF-B, and AP-1.Acute pancreatitis (AP) is the rapid onset of inflammation of the pancreas. The severity of the disease varies widely, because mild forms of acute pancreatitis are self-limiting and the more severe forms could result in multiple organ dysfunction. It is thought that the initiating event of AP is the injury of enzyme-secreting pancreatic acinar cells (Bhatia, 2005). Injured tissue releases cytokines and chemokines, which then leads to a worsening of inflammatory response. The pathophysiology of AP has largely been determined using cellular and animal models of AP. The endogenous hormone cholecystokinin (CCK) or its amphibian ortholog caerulein is often used to induce experimental AP. The concentration of caerulein that mimics physiological concentration is reported to be 10 Ϫ10 M, whereas a supraphysiological concentration of 10 Ϫ7 M is often used to mimic AP in cellular models (Thrower et al., 2008).The binding of substance P (SP) to its receptor, neurokinin-1 receptor (NK1R), was found to be crucial in determining the outcome of AP (Pandol et al., 2007). SP belongs to the tachykinin neuropeptide family and is derived from the product of preprotachykinin-A (PPT-A) gene. SP is mainly produced by neural cells, but other cell types, such as mouse pancreatic acinar cells, are known to express both SP and NK1R (Tamizhselvi et al., 2007). Stimulation of pancreatic acinar cells with SP was found to up-regulate the production

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Section: Discussionsupporting

confidence: 92%

Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells

Koh

Tamizhselvi²,

Bhatia³

2009

J Pharmacol Exp Ther

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“…We focused on ATF-2, for two reasons. First, NF-B activation has been well documented in gliomas (33)(34)(35)(36)(37), and second, our prior inhibitor studies indicated that the inhibition of p38 (Fig. 2) significantly diminished the IL-1 induction of TIMP-1 in astrocytes.…”

Section: Timp-1 Expression Is Not Activated By Il-1 In Many Gliomas Bmentioning

confidence: 82%

A Novel Mechanism of Tissue Inhibitor of Metalloproteinases-1 Activation by Interleukin-1 in Primary Human Astrocytes

Wilczynska

Gopalan

Bugno

et al. 2006

Journal of Biological Chemistry

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Reactive astrogliosis is the gliotic response to brain injury with activated astrocytes and microglia being the major effector cells. These cells secrete inflammatory cytokines, proteinases, and proteinase inhibitors that influence extracellular matrix (ECM) remodeling. In astrocytes, the expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) is up-regulated by interleukin-1 (IL-1), which is a major neuroinflammatory cytokine. We report that IL-1 activates TIMP-1 expression via both the IKK/NF-B and MEK3/6/p38/ATF-2 pathways in astrocytes. The activation of the TIMP-1 gene can be blocked by using pharmacological inhibitors, including BAY11-7082 and SB202190, overexpression of the dominant-negative inhibitor of NF-B (IB␣SR), or by the knock-down of p65 subunit of NF-B. Binding of activated NF-B (p50/p65 heterodimer) and ATF-2 (homodimer) to two novel regulatory elements located ؊2.7 and ؊2.2 kb upstream of the TIMP-1 transcription start site, respectively, is required for full IL-1-responsiveness. Mutational analysis of these regulatory elements and their weak activity when linked to the minimal tk promoter suggest that cooperative binding is required to activate transcription. In contrast to astrocytes, we observed that TIMP-1 is expressed at lower levels in gliomas and is not regulated by IL-1. We provide evidence that the lack of TIMP-1 activation in gliomas results from either dysfunctional IKK/NF-B or MEK3/6/p38/ATF-2 activation by IL-1. In summary, we propose a novel mechanism of TIMP-1 regulation, which ensures an increased supply of the inhibitor after brain injury, and limits ECM degradation. This mechanism does not function in gliomas, and may in part explain the increased invasiveness of glioma cells.The remodeling of the extracellular matrix (ECM), 2 including the degradation of the ECM by matrix metalloproteinases (MMPs) and its subsequent resynthesis, is critical during normal physiological processes, such as angiogenesis, embryonic development, organ morphogenesis, bone remodeling, and ovulation (1, 2). During these processes the proteolytic activity of MMPs is tightly controlled at the transcriptional level by growth factors, hormones, and cytokines, and at the protein level by proteolytic cleavage of inactive zymogens, and the inhibition by specific inhibitors, including tissue inhibitors of metalloproteinases (TIMPs) (2). The delicate balance between the activities of MMPs and TIMPs is critical to limit deleterious outcomes of uncontrolled degradation, which is manifested in pathological conditions such as periodontal disease, arthritis, tumor cell invasion, fibrosis, and neurodegenerative disorders (2-4). These pathological conditions often represent chronic inflammatory diseases suggesting that inflammatory mediators, including inflammatory cytokines, may disrupt the intricate balance between MMPs and TIMPs.In the central nervous system (CNS), infection and injury induce a histopathological response known as reactive astrogliosis, which is the primary cause of regenerative failure in ...

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“…These animals were housed in a temperaturecontrolled room (23)(24)(25) C). They were maintained in individual cages under a light/dark cycle (lights on at 0800, lights off at 2000) and were given free access to food and water.…”

Section: Methodsmentioning

confidence: 99%

Morphological Interrelationship Between Astrocytes and Nerve Endings in the Rat Spinal Trigeminal Nucleus Caudalis

Zhang¹,

Tamada

Akai

et al. 2006

Okajimas Folia Anat. Jpn.

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Summary: It has been reported that the spinal trigeminal nucleus caudalis (Sp5C), which receives nociceptive information from the oro-facial regions, has four laminae. To clarify the role of glial cells in the transmission of the nociceptive information, the present study was conducted to examine the detailed distribution of astrocytes in each lamina and also to investigate a morphological interrelationship between the astrocytes and nerve endings in the rat Sp5C. After the preparation of the serial cryostat sections, immunohistochemistry for glial fibrillary acidic protein (GFAP) was employed to identify the astrocytes, and immunohistochemistry for substance P (SP), calcitonin gene-related peptide (CGRP), was used for the nerve endings. We also employed double-labeling immunofluorescence and electron microscopic immunohistochemistry for the GFAP/SP or GFAP/CGRP. GFAP-positive reactions were observed in all laminae of the Sp5C, and SP-or CGRP-positive nerve endings were observed in the lamina I and II. Additionally, we clarified the presence of GFAP/SP-or GFAP/CGRP-positive reactions by the double-labeling immunofluorescence and demonstrated the morphological interrelationship between the astrocytes and nerve endings by the double-labeling electron microscopic immunohistochemistry. These findings suggest that astrocytes might play some roles in the transmission of nociceptive information from the oro-facial region.

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Interleukin‐1β upregulates functional expression of neurokinin‐1 receptor (NK‐1R) via NF‐κB in astrocytes

Cited by 59 publications

References 50 publications

Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells

Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells

A Novel Mechanism of Tissue Inhibitor of Metalloproteinases-1 Activation by Interleukin-1 in Primary Human Astrocytes

Morphological Interrelationship Between Astrocytes and Nerve Endings in the Rat Spinal Trigeminal Nucleus Caudalis

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Interleukin‐1β upregulates functional expression of neurokinin‐1 receptor (NK‐1R) via NF‐κB in astrocytes

Cited by 59 publications

References 50 publications

Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH2-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells

Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH2-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells

A Novel Mechanism of Tissue Inhibitor of Metalloproteinases-1 Activation by Interleukin-1 in Primary Human Astrocytes

Morphological Interrelationship Between Astrocytes and Nerve Endings in the Rat Spinal Trigeminal Nucleus Caudalis

Contact Info

Product

Resources

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Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells

Extracellular Signal-Regulated Kinase 1/2 and c-Jun NH₂-Terminal Kinase, through Nuclear Factor-κB and Activator Protein-1, Contribute to Caerulein-Induced Expression of Substance P and Neurokinin-1 Receptors in Pancreatic Acinar Cells