Induction and Expression of β-Calcitonin Gene-Related Peptide in Rat T Lymphocytes and Its Significance

Xing, Liyu; Guo, Jun; Wang, Xian

doi:10.4049/jimmunol.165.8.4359

Cited by 58 publications

(35 citation statements)

References 33 publications

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“…2). However, recent studies (2,3,42) reported that activated immune cells can produce neuropeptides such as SP, calcitonin gene-related peptide, and HT-29 monolayers were grown to confluence and then cultured in DMEM containing 0.1% FCS for 24 h. Cells were then incubated for an additional 3-24 h in medium alone or containing NT (10 Ϫ8 M). Total RNA was extracted, and 1 g was used to prepare cDNAs; COX-2 mRNA levels were determined by quantitative RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

Brun¹,

Mastrotto²,

Beggiao³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Because neurotensin (NT) and its highaffinity receptor (NTR1) modulate immune responses, chloride secretion, and epithelial cell proliferation, we sought to investigate their role in the repair process that follows the development of mucosal injuries during a persistent inflammation. Colonic NT and NTR1, mRNA, and protein significantly increased only after dextran sodium sulfate (DSS)-induced inflammatory damage developed. Colitis-induced body weight loss, colonic myeloperoxidase activity, and histological damage were significantly enhanced by SR-48642 administration, a nonpeptide NTR1 antagonist, whereas continuous NT infusion ameliorated colitis outcome. To evaluate the NT and NTR1 role in tissue healing, mucosal inflammatory injury was established administering 3% DSS for 5 days. After DSS discontinuation, mice rapidly gained weight, ulcers were healed, and colonic NT, NTR1, and cyclooxygenase (COX)-2 mRNA levels were upregulated, whereas SR-48642 treatment caused a further body weight loss, ulcer enlargement, and a blunted colonic COX-2 mRNA upregulation. In a woundhealing model in vitro, NT-induced cell migration in the denuded area was inhibited by indomethacin but not by an antitransforming growth factor-␤ neutralizing antibody. Furthermore, NT significantly increased COX-2 mRNA levels by 2.4-fold and stimulated PGE2 release in HT-29 cells. These findings suggest that NT and NTR1 are part of the network activated after mucosal injuries and that NT stimulates epithelial restitution at least, in part, through a COX-2 dependent pathway. neurotensin receptor type 1; healing; colitis; cyclooxygenase-2; inflammatory bowel disease INFLAMMATORY BOWEL DISEASE (IBD) is a chronic intestinal inflammatory disorder that is considered the consequence of an aberrant response of the immune system to luminal antigens (13). Although the event(s) triggering the chronic inflammatory disorder has not been identified, a variety of cells and soluble factors mediate the extended mucosal damage (13). However, after the development of mucosal injuries, the intestinal epithelium rapidly tends to reestablish its integrity (26). To reestablish mucosal integrity, epithelial cells migrate into the wounded area (epithelial restitution), and they then proliferate to replace the decreased cell pool. Studies over the past several years have shown that a variety of soluble peptides, prostaglandins, growth factors, and cytokines are secreted in a

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Section: Discussionmentioning

confidence: 99%

Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

Brun¹,

Mastrotto²,

Beggiao³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

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“…6B). SP and CGRP are released from sensory nerves when TRPV1 is activated, but they are also present in resident macrophages and circulating leukocytes (27)(28)(29). Indeed, SP treatment has been shown to stimulate macrophage- mediated phagocytosis in vitro (30).…”

Section: Trpv1 Deletion Affects Phagocytosis Via the Nk 1 Receptor Fomentioning

confidence: 99%

TRPV1 Deletion Enhances Local Inflammation and Accelerates the Onset of Systemic Inflammatory Response Syndrome

Fernandes

Liang

Smillie

et al. 2012

The Journal of Immunology

119

126

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The transient receptor potential vanilloid 1 (TRPV1) is primarily localized to sensory nerve fibers and is associated with the stimulation of pain and inflammation. TRPV1 knockout (TRPV1KO) mice show enhanced LPS-induced sepsis compared with wild type (WT). This implies that TRPV1 may have a key modulatory role in increasing the beneficial and reducing the harmful components in sepsis. We investigated immune and inflammatory mechanisms in a cecal ligation and puncture (CLP) model of sepsis over 24 h. CLP TRPV1KO mice exhibited significant hypothermia, hypotension, and organ dysfunction compared with CLP WT mice. Analysis of the inflammatory responses at the site of initial infection (peritoneal cavity) revealed that CLP TRPV1KO mice exhibited: 1) decreased mononuclear cell integrity associated with apoptosis, 2) decreased macrophage tachykinin NK1-dependent phagocytosis, 3) substantially decreased levels of nitrite (indicative of NO) and reactive oxygen species, 4) increased cytokine levels, and 5) decreased bacteria clearance when compared with CLP WT mice. Therefore, TRPV1 deletion is associated with impaired macrophage-associated defense mechanisms. Thus, TRPV1 acts to protect against the damaging impact of sepsis and may influence the transition from local to a systemic inflammatory state.

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“…␣CGRP is produced mainly in the nervous system by the tissue-specific alternative splicing of the primary RNA transcript of the calcitonin/CGRP gene. On the other hand, ␤CGRP is produced not only in the neuronal tissues but also in the enteric nerves of the intestine (2) and in immune cells such as T cells (3). Pharmacologically, ␣CGRP is known to have the most potent vasodilatory activity (4).…”

mentioning

confidence: 99%

Hypertension and dysregulated proinflammatory cytokine production in receptor activity-modifying protein 1-deficient mice

Tsujikawa

Yayama

Hayashi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

122

132

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Calcitonin gene-related peptide (CGRP) is thought to be a prominent neuropeptide in cardiovascular regulation and neuroimmune modulation. There are two isoforms of CGRP (␣CGRP and ␤CGRP), and the main CGRP receptors are probably composed of a calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP)1. However, the physiological functions of CGRP that are mediated through the CLR/RAMP1 receptors remain to be clarified. For an improved understanding of the functions, we generated mice deficient in RAMP1, a specific subunit of CGRP receptors, by a conditional gene-targeting technique. The RAMP1-deficient mice (RAMP1 ؊/؊ ) exhibited high blood pressure, with no changes in heart rate. ␣CGRP was found to have a potent vascular relaxant activity compared with ␤CGRP in the artery of the WT (RAMP1 ؉/؉ ) mice. The activities of both CGRP isoforms were remarkably suppressed in the arteries of the RAMP1 ؊/؊ mice. The LPS-induced inflammatory responses of the RAMP1 ؊/؊ mice revealed a transient and significant increase in the serum CGRP levels and high serum levels of proinflammatory cytokines compared with the RAMP1 ؉/؉ mice. ␣CGRP and ␤CGRP equally suppressed the production of TNF-␣ and IL-12 in bone marrow-derived dendritic cells stimulated with lipopolysaccharide. Their inhibitory effects were not observed in the bone marrow-derived dendritic cells of the RAMP1 ؊/؊ mice. These results indicate that CGRP signaling through CLR/RAMP1 receptors plays a crucial role in the regulation of both blood pressure by vascular relaxation and proinflammatory cytokine production from dendritic cells.gene-disrupted mice ͉ calcitonin gene-related peptide ͉ adrenomedullin ͉ neuropeptide ͉ dendritic cells C alcitonin gene-related peptide (CGRP) is a 37-aa neuropeptide that is produced in the neural body of dorsal root ganglion cells and released from sensory nerve endings. There are two isoforms of CGRP: ␣ and ␤ in rats and mice and I and II in humans. These differ in their peptide sequences by 1 aa (rats) and 3 aa (mice and humans) of the 37 aa (1). ␣CGRP is produced mainly in the nervous system by the tissue-specific alternative splicing of the primary RNA transcript of the calcitonin/CGRP gene. On the other hand, ␤CGRP is produced not only in the neuronal tissues but also in the enteric nerves of the intestine (2) and in immune cells such as T cells (3). Pharmacologically, ␣CGRP is known to have the most potent vasodilatory activity (4). Most blood vessels are surrounded by a dense perivascular CGRPergic neural network, suggesting the physiological importance of CGRP in vasodilatory regulation (5). ␣CGRP also contributes to local neurogenic inflammation and nociception (6). Moreover, the functions of immune cells such as macrophages (7,8), Langerhans cells (8), and T cells (9, 10) are modulated by ␣CGRP. However, the precise functional differences between ␣CGRP and ␤CGRP remain unclear.Historically, CGRP receptors have been classified into two classes: CGRP 1 and CGRP 2 receptors. The CGRP 1 receptors are m...

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Induction and Expression of β-Calcitonin Gene-Related Peptide in Rat T Lymphocytes and Its Significance

Cited by 58 publications

References 33 publications

Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

TRPV1 Deletion Enhances Local Inflammation and Accelerates the Onset of Systemic Inflammatory Response Syndrome

Hypertension and dysregulated proinflammatory cytokine production in receptor activity-modifying protein 1-deficient mice

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