Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease

Yamamoto, Hitoshi; Morise, Kimitomo; Kusugami, Kazuo; Furusawa, Atsushi; Konagaya, Toshihiro; Nishio, Yuji; Kaneko, Hiroshi; Uchida, Kiyoshi; Nagai, Hirofumi; Mitsuma, Terunori; Nishimura, Hiroshi

doi:10.1007/bf02355052

Cited by 51 publications

(39 citation statements)

References 37 publications

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“…NKA has also been shown to play an important role in neurogenic inflammation in several conditions. Indeed neurogenic inflammation likely underlies several disease conditions (20), such as asthma (15,27), immunecomplex-mediated lung injury (7), experimental arthritis (40), and inflammatory bowel disease (41). Based on our studies with NK1 receptor knockout mice, we pre- viously proposed a proinflammatory contribution of substance P in the pathogenesis of acute pancreatitis and associated lung injury (8).…”

Section: Discussionmentioning

confidence: 97%

“…Substance P is released from nerve endings in many tissues. Subsequent to its release, substance P binds primarily, but not exclusively, to NK1 receptors on the surface of effector cells and, in addition to being a mediator of pain, acts as a proinflammatory mediator in many inflammatory states (20) including asthma (15,27), immune-complex-mediated lung injury (7), experimental arthritis (40), and inflammatory bowel disease (41). NKA binds primarily to NK2 receptors.…”

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confidence: 99%

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Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Bhatia

Slavin

Cao

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Preprotachykinin-A (PPT-A) gene products substance P and neurokinin (NK)-A have been shown to play important roles in neurogenic inflammation. Substance P acts primarily (but not exclusively) via the NK1 receptor. NKA acts primarily via the NK2 receptor. Earlier work has shown that knockout mice deficient in NK1 receptors are protected against acute pancreatitis and associated lung injury. NK1 receptors, however, bind other peptides in addition to substance P, not all of which are derived from the PPT-A gene. To examine the role of PPT-A gene products in acute pancreatitis, the effect of PPT-A gene deletion on the severity of acute pancreatitis and the associated lung injury was investigated. Deletion of PPT-A almost completely protected against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage. These results show that PPT-A gene products are critical proinflammatory mediators in acute pancreatitis and the associated lung injury.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Bhatia

Slavin

Cao

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…While SP is abundant in the intestines, there are somewhat conflicting data regarding the concentration of SP in the intestinal mucosa of patients with IBD (37)(38)(39). Some studies report high levels that correlate with the activity of the disease (38 -40).…”

Section: Discussionmentioning

confidence: 99%

Substance P Regulates Th1-Type Colitis in IL-10 Knockout Mice

Weinstock

Blum

Metwali

et al. 2003

The Journal of Immunology

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Substance P (SP) is a proinflammatory molecule that interacts with a neurokinin 1 receptor (NK-1R), which is on T cells and helps control IFN-γ production. IL-10−/− mice given a nonsteroidal anti-inflammatory drug (NSAID) develop Th1 colitis. We studied the importance of SP and NK-1R in this colitis model. LP T cells were isolated to study their NK-1R expression. LP T cells from IL-10−/− mice expressed NK-1R and produced IFN-γ only after NSAID treatment and induction of colitis. LP T cells from NSAID-treated wild-type controls or from age-matched untreated IL-10−/− animals did not express NK-1R or produce IFN-γ. Experiments showed that IL-12 induced NK-1R transcription in CD4+ T cells cultured in vitro. However, T cells cultured with IL-12 and IL-10 did not express NK-1R. IL-10 also down-modulated ongoing NK-1R expression. Mice given NK-1R antagonist after NSAID induction of severe colitis showed nearly complete reversal of inflammation, and LP T cells ceased IFN-γ secretion. Thus, intestinal inflammation in IL-10−/− mice is associated with the appearance of NK-1R in mucosal T cells, and an interplay between IL-12 and IL-10 regulates T cell NK-1R transcription. NK-1R antagonist reverses ongoing intestinal inflammation attesting to the importance of SP and its receptor in mucosal inflammation.

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“…There is evidence suggesting neuropeptides, such as SP and its receptors, play a significant role in initiating and modulating GI inflammation. A marked increase in both the colonic mucosal SP concentration and SP binding sites on mucosal blood vessels and lymphoid tissue in patients with ulcerative colitis (29,47) has been observed. Other reports (35) have implicated SP in acute inflammation of the ileum induced by Clostridium difficile.…”

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confidence: 98%

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Hassani

Lucas

Rozell

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Neuropeptide Y (NPY), a 36-amino acid peptide, is widely expressed in the central and peripheral nervous system. NPY is involved in the regulation of several physiological processes, including energy balance, food intake, and nociception. Recently, we showed that activation of the NPY Y1 receptor is required for cutaneous neurogenic inflammation. Because neurogenic inflammation could participate in colitis, the aim of this study was to investigate the role of the NPY Y1 receptor in acute colitis using mice genetically deficient of NPY Y1 receptor. In addition, the Y1 receptor antagonist H409/22, was also investigated. Animals received 5% dextran sulfate sodium (DSS) in drinking water for 7 days. One group of animals also received the Y1 receptor antagonist, administered intraperitoneally twice daily. Disease activity was assessed daily for 7 days in all groups. DSS induced colitis in all animals resulting in weight loss, diarrhea, epithelial damage, crypt shortening, and inflammatory infiltration. However, clinical manifestation of the disease was markedly attenuated in Y1 null mutant mice as well as in mice receiving the Y1 antagonist. Histological analysis showed that tissue damage and ulceration were less severe in Y1-deficient animals. Consistent with the clinical and histological data, capsaicin-induced plasma extravasation was significantly reduced in the gut of Y1 null mutant animals compared with treated wild-type animals. These data indicate that NPY and Y1 receptor are involved in intestinal inflammation and suggest that inhibition of NPY Y1 receptor signaling may provide a novel therapeutic approach in the treatment of colonic inflammation. neurogenic inflammation; dextran sulfate sodium; in vivo animal models ULCERATIVE COLITIS AND CROHN'S disease constitute the two main forms of inflammatory bowel disease (IBD). This disease is characterized by a dysregulated immune response and chronic relapsing inflammation of the gastrointestinal (GI) tract, leading to diarrhea, hemoccult, abdominal pain, weight loss, and anemia.Despite intense research, the etiology of IBDs remains largely unknown. The development of IBD involves interactions among genetic, immunological, and environmental components (46). Other mediators implicated in the pathogenesis of colitis are neuropeptides released from enteric and sensory afferent neurons (37). These peptides have been shown to modulate different aspects of mucosal function, including blood flow and secretion, and may play a role in the recruitment of granulocytes and lymphocytes and in the modulation of mast cell activation (14,18).Stimulation and activation of capsaicin-sensitive sensory nerve endings produce an inflammatory response characterized by vasodilation and plasma extravasation (13). The inflammatory response is mediated by local release of sensory neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) (25). The inflammatory response, termed neurogenic inflammation, is well described in many peripheral organs including the skin, ai...

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Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease

Cited by 51 publications

References 37 publications

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Substance P Regulates Th1-Type Colitis in IL-10 Knockout Mice

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

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