Neurotensin modulates human neutrophil locomotion and phagocytic capability

Goldman, Rachel; Bar‐Shavit, Zvi; Romeo, Domenico

doi:10.1016/0014-5793(83)80417-7

Cited by 45 publications

(23 citation statements)

References 24 publications

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“…It is likely that the COX-2-independent increase in proliferative capacity demonstrated by NMCM-cultured intestinal epithelial cells is related to 'conditioning' of medium with mitogenic factors by non-activated RAW264.7 macrophages (Rosenberger et al, 2000). This phenomenon has been described in models using a variety of target cells (Goldman and Bar-Shavit, 1979;Hauptmann et al, 1993). In keeping with our observations that macrophage COX-2 activity promotes intestinal epithelial cell proliferation in vitro, Sonoshita et al (2001) have recently reported that stromal cell COX-2 drives increased epithelial cell proliferation in Apc D716 mouse adenomas.…”

Section: Discussionmentioning

confidence: 98%

Paracrine cyclooxygenase-2-mediated signalling by macrophages promotes tumorigenic progression of intestinal epithelial cells

Chapple

Hawcroft

et al. 2002

Oncogene

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In human colorectal adenomas or polyps, cyclooxygenase-2 is expressed predominantly by stromal (or interstitial) macrophages. Therefore, we tested the hypothesis that macrophage cyclooxygenase-2 has paracrine pro-tumorigenic activity using in vitro models of macrophage-epithelial cell interactions. We report that macrophages can promote tumorigenic progression of intestinal epithelial cells (evidenced by decreased cellcell contact inhibition, increased proliferation and apoptosis, gain of anchorage-independent growth capability, decreased membranous E-cadherin expression, up-regulation of cyclooxygenase-2 expression, down-regulation of transforming growth factor-b type II receptor expression and resistance to the antiproliferative activity of transforming growth factor-b 1 ) in a paracrine, cyclooxygenase-2-dependent manner. Pharmacologically relevant concentrations (1 -2 mM) of a selective cyclooxygenase-2 inhibitor had no detectable, direct effect on intestinal epithelial cells but inhibited the macrophage-epithelial cell signal mediating tumorigenic progression. Cyclooxygenase-2-mediated stromal-epithelial cell signalling during the early stages of intestinal tumorigenesis provides a novel target for chemoprevention of colorectal cancer (and other gastro-intestinal epithelial malignancies, which arise on a background of chronic inflammation, such as gastric cancer) and may explain the discrepancy between the concentrations of cyclooxygenase inhibitors required to produce antineoplastic effects in vitro and in vivo.

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Section: Discussionmentioning

confidence: 98%

Paracrine cyclooxygenase-2-mediated signalling by macrophages promotes tumorigenic progression of intestinal epithelial cells

Chapple

Hawcroft

et al. 2002

Oncogene

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“…NT regulates several biological processes, such as intestinal motility, secretion, vascular smooth muscle activity, and intestinal epithelial cell proliferation, but recent evidence indicates that in NT there is also a potent neuroimmunomodulator (43). Thus NT interacts with leukocytes, mast cells, and macrophages, inducing cytokine release and enhancing chemotaxis (14,16,21). Recent in vivo evidence supports the view that NT may be involved in acute and chronic inflammatory disorders.…”

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confidence: 90%

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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“…NT also interacts in vitro with immune and inflammatory cells, including leukocytes (10), peritoneal mast cells (7), and macrophages (11,12). Although these studies point to a role for NT in inflammatory reactions, the possibility that this peptide participates in the pathogenesis of colonic inflammation has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

Castagliuolo¹,

Wang²,

Valenick³

et al. 1999

J. Clin. Invest.

130

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A growing body of evidence suggests that interaction of epithelial and immune cells via neuropeptides, hormones, and cytokines participate in the pathophysiology of diarrhea and intestinal inflammation (reviewed in ref. 1). Neurotensin (NT), a bioactive peptide (2) with a primary distribution in the brain and the gastrointestinal tract, has been localized by immunohistochemistry to endocrine cells (N cells) and neurons in the intestinal mucosa, submucosa, and muscularis of animals and humans (3). A wide range of biological activities has been described for NT with actions on the cardiovascular, gastrointestinal, reproductive, and central nervous systems (3). The known intestinal effects of this peptide include trophic effects on small and large bowel, pancreas, and stomach; inhibition of small bowel and gastric motility; and stimulation of colonic motor activity (3). Studies in animals (3, 4, 5) and humans (3, 6) also demonstrate that NT may modulate fluid secretion in the intestinal tract and that its secretory effects in the ileum may be mediated through a nervous reflex in the enteric nervous system (5).Several lines of evidence indicate that NT may also participate in inflammatory reactions. Intravenous administration of NT to rats causes mast cell degranulation (7) and increases vascular permeability and levels of histamine and leukotriene C4 in the plasma (8); these effects can be inhibited by a specific NT receptor antagonist (9).NT also interacts in vitro with immune and inflammatory cells, including leukocytes (10), peritoneal mast cells (7), and macrophages (11,12). Although these studies point to a role for NT in inflammatory reactions, the possibility that this peptide participates in the pathogenesis of colonic inflammation has not been examined.NT exerts its effects by interacting with specific receptors (NTR) on cell surfaces. Two specific receptors for NT (NTR1 and NTR2), which belong to the seven transmembrane G protein-linked superfamily, have been identified and cloned (13,14). NTR1-mRNA and NT binding sites have been identified in the brain (15), small and large intestine of animals and humans (13, 15), human colonic epithelial cell lines (16,17), human blood mononuclear cells (11), and endothelial cells (18). Recently, we demonstrated the presence of NTR1 mRNA in the rat colonic mucosa, including colonic epithelial cells (19). We also showed that administration of the specific NT receptor nonpeptide antagonist SR-48,692 to rats attenuated colonic mucin secretion and mast cell activation following immobilization stress, indicating a critical role for NT in stress-related colonic responses (19).Clostridium difficile is the primary pathogenic factor of antibiotic-associated diarrhea in humans and animals The neuropeptide neurotensin mediates several intestinal functions, including chloride secretion, motility, and cellular growth. However, whether this peptide participates in intestinal inflammation is not known. Toxin A, an enterotoxin from Clostridium difficile, mediates pseudomembranous col...

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Neurotensin modulates human neutrophil locomotion and phagocytic capability

Cited by 45 publications

References 24 publications

Paracrine cyclooxygenase-2-mediated signalling by macrophages promotes tumorigenic progression of intestinal epithelial cells

Paracrine cyclooxygenase-2-mediated signalling by macrophages promotes tumorigenic progression of intestinal epithelial cells

Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation

Neurotensin is a proinflammatory neuropeptide in colonic inflammation

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