Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells represent significant cellular element of the skin. It is now postulated that they play an important role in cutaneous homeostasis and are engaged in some pathological processes as well. The aim of our study was to examine sensitivity of human cutaneous mast cells to anaphylactic and anaphylactoid stimuli. The studies were performed on human cutaneous mast cells obtained from healthy skin by enzymatic dispersion technique. The mast cells were activated in vitro with anti-IgE, concanavalin A (Con A), compound 48/80, substance P (SP) or tumor necrosis factor alpha (TNF-alpha). We have noticed that skin mast cells were susceptible to the challenge with anti-IgE and Con A, and histamine release was dose- and time-dependent. In both cases histamine release was high (44.0 +/- 4.1% with anti-IgE at dilution 1:500 and 20.1 +/- 2.4% with Con A in concentration 500 micrograms/ml). Cutaneous mast cells were challenged in a dose- and time-related fashion with compound 48/80, however histamine release was low (9.8 +/- 2.4%, at concentration of compound 48/80-100 micrograms/ml). SP and TNF-alpha also activated mast cells but the magnitude of histamine release was not high (up to 7.1 +/- 0.9%, SP in concentration 10(-4) M and 17.4 +/- 1.1%, TNF-alpha in concentration 10(-6) M) and maximal after 20 min reaction.
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PMID:Sensitivity of human cutaneous mast cells to anaphylactic and nonimmunological stimuli. 909 Apr 41

Substance P (SP) has been shown to mediate granulocyte infiltration into the mouse skin by inducing mast cell degranulation. In this study, using a variety of specific inhibitors, we investigated the cascade of events involved in the response of neutrophils and eosinophils to SP. The prostaglandin inhibitor, indomethacin, had little effect on SP-induced leukocyte migration. In contrast, pretreatment with the leukotriene (LT) synthesis inhibitor, A-64077, completely blocked neutrophil but not eosinophil migration in response to SP. Participation of tumor necrosis factor alpha (TNF-alpha) and LFA-1/ICAM-1 interaction was confirmed by inhibition of SP-induced leukocyte migration by pretreatment of mice with monoclonal antibodies to TNF-alpha, LFA-1, and ICAM-1. Moreover, alteration in leukocyte migration by indomethacin was found to depend on the concentration of TNF-alpha used. Indomethacin did not alter the number of leukocytes induced by low concentrations of TNF-alpha (0.1 ng), but reduced the number of cells stimulated with high TNF-alpha concentrations (1.0 ng). These results support the concept that SP modulates in vivo neuroinflammatory responses, as measured by granulocyte migration, initiating a cascade of events that includes LT production, TNF-alpha secretion, and engagement of LFA-1 and ICAM-1.
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PMID:Involvement of leukotrienes, TNF-alpha, and the LFA-1/ICAM-1 interaction in substance P-induced granulocyte infiltration. 910 31

Previously we reported that pretreatment of rats with the substance P (SP) antagonist CP-96,345 inhibits the enterotoxic responses following administration of toxin A from Clostridium difficile into ileal loops, indicating that SP participates in the intestinal responses to this toxin. We now report that injection of toxin A into rat ileum causes a rapid increase in SP content in lumbar dorsal root ganglia (DRG) and mucosal scrapings 30-60 min after toxin A administration. Toxin A-mediated fluid secretion, mannitol permeability, and ileal histologic damage is significantly increased only after 2 hr. Toxin A also causes an increase in the abundance of SP mRNA in lumbar DRG and ileal mucosa as measured by reverse transcription-PCR. Lamina propria macrophages (LPMs) obtained from toxin A-injected loops release greater amounts of tumor necrosis factor alpha (TNFalpha) and SP as compared with LPMs isolated from buffer-injected loops (P < 0.01). Pretreatment of rats with the SP antagonist CP-96,345 inhibits toxin A-mediated TNFalpha release from isolated LPMs, whereas an inactive enantiomer (CP-96,344) of the SP antagonist has no effect. LPMs obtained from toxin A-injected ileal loops incubated in vitro with SP (10(-8) to 10(-9) M) show enhanced TNFalpha secretion, whereas LPMs isolated from buffer-injected loops do not respond to SP. In addition, LPMs obtained from toxin A-injected ileal loops incubated in vitro with CP-96,345 showed a diminished TNFalpha release. Our results indicate that activated LPMs secrete SP during toxin A enteritis that can lead to secretion of cytokines, suggesting an autocrine/paracrine regulation of cytokine secretion by SP from LPMs during intestinal inflammation.
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PMID:Increased substance P responses in dorsal root ganglia and intestinal macrophages during Clostridium difficile toxin A enteritis in rats. 911 70

In order to identify possible functional differences between mast cells obtained from the skin of lichen planus (LP) patients and healthy donors, biopsies from lesional skin of 11 lichen planus patients and from normal skin of 7 healthy donors were sampled. Mast cells were obtained from the skin using an enzymatic dispersion technique. The cells were challenged in vitro with substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE. Their reactivity was estimated on the basis of histamine release. LP skin mast cells and healthy skin mast cells showed similar sensitivity to stimulation with TNF-alpha at a concentration of 10(-7) M (15.2% histamine release, as a proportion of total cellular content vs 15.9%) and to stimulation with anti-IgE at a dilution of 1:100) (38.8% vs 37.0%). Spontaneous histamine release was also very similar in both the populations of mast cells (10.2% vs 12.7%, respectively). However, LP skin mast cells showed significantly higher (P < 0.01) sensitivity towards stimulation with SP at a concentration of 10(-4) M than healthy skin mast cells (15.9% histamine release vs 7.0%). This finding could suggest that neurogenic inflammatory mechanisms contribute to the pathogenesis of LP.
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PMID:Functional studies of skin mast cells in lichen planus. 916 35

There is increasing experimental evidence that the neurologic system can directly participate in cutaneous inflammation and wound healing. Recent studies indicate that neuropeptides released by cutaneous nerves such as c-fibers can activate a number of target cells including keratinocytes, Langerhans cells, mast cells, and endothelial cells. One such neuropeptide, substance P (SP), is able to specifically bind to murine and human keratinocytes and induce the release of cytokines such as interleukin 1 (IL-1). Other studies demonstrate that SP can also activate mast cells to produce the potent pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha). More recently, we examined the effect of cutaneous neuropeptides on human dermal microvascular endothelial cell (HDMEC) activities. Our studies indicate that the c-fiber-derived calcitonin gene-related peptide (CGRP) is capable of stimulating HDMEC to secrete the neutrophil chemotactic factor interleukin 8 (IL-8). In addition, SP is able to directly activate HDMEC to express high levels of the important cellular adhesion molecule vascular cellular adhesion molecule 1 (VCAM-1). Thus, these studies support the role that the neurologic system may play in mediating the biologic processes that occur during inflammation and wound healing in the skin.
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PMID:Interactions of the skin and nervous system. 948 11

The aim of our study was to evaluate the sensitivity of skin mast cells from urticaria pigmentosa (UP) patients to substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE, and to compare the sensitivity of these cells with that of skin mast cells from healthy human donors. Mast cells for in vitro functional studies were obtained using an enzymatic dispersion technique from skin biopsies (from 11 patients with UP and 11 healthy donors), and the reactivity of these cells was estimated on the basis of histamine release. Our observations indicated that UP skin mast cells and healthy skin mast cells had similar sensitivities to challenge with TNF-alpha at a concentration 10(-7) M (16.4% vs 15.2%) and with anti-IgE at a dilution 1:100 (41.0% vs 37.0%). However, UP mast cells showed considerably higher sensitivity to challenge with SP at a concentration 10(-4) M than healthy skin mast cells (20.0% vs 6.8%), and the difference was statistically significant (P < 0.001). UP skin mast cells also demonstrated significantly higher spontaneous histamine release than healthy skin mast cells (32.1% vs 12.4%, P < 0.001). Our findings indicating UP skin mast cell sensitivity to SP might suggest that mechanisms involving neurogenic inflammation could contribute to the course of this disease.
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PMID:In vitro reactivity of mast cells in urticaria pigmentosa skin. 952 96

Severe traumatic injuries and infections are frequently accompanied by life-threatening shock and are associated with increases in the proinflammatory cytokines, particularly tumor necrosis factor alpha (TNF-alpha). The body's first perception of injury is the nociceptive or pain response. This response is induced at the site of injury and is transmitted systemically by sensory neuropeptides, the tachykinins, released from sensory afferent c-fiber neurons. We studied the role of tachykinins in regulating the production of proinflammatory cytokines induced by the administration of bacterial lipopolysaccharide. Destruction of terminal sensory nerve endings before lipopolysaccharide administration abrogates tachykinin synthesis and down-regulates TNF-alpha transcription and secretion. In contrast, the responses of interleukins-1 and -6 are unaffected. Pretreating animals with an antagonist for the substance P-specific NK-1 receptor also down-regulated the TNF-alpha response, whereas blockade of the NK-2 receptor had no effect. These findings indicate that substance P contributes to the induction of those cytokines that are involved in precipitating the shock response.
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PMID:Neuropeptide regulation of proinflammatory cytokine responses. 958 4

Neurogenic inflammation of the skin observed after topical application of an irritant substance or environmental stimulation induces vascular changes and the production of inflammatory mediators. Substance P (SP) is one of the main neuropeptides which trigger an inflammatory response in the skin. So, with the aim to develop an alternative method to study neurogenic inflammation of the skin, we used an organ culture of human skin. SP was added onto epidermis or directly to culture medium in an attempt to reproduce ex vivo the effects described in vivo. Even disconnected from systemic blood circulation, in skin fragments in culture, we observed dose-dependent edema, vasodilation and extravasation of lymphocytes and mast cells through the microvascular wall. Moreover, the release of proinflammatory mediators interleukin 1alpha and tumor necrosis factor alpha was evidenced.
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PMID:Neurogenic modifications induced by substance P in an organ culture of human skin. 1042 Jan 41

We found that substance P (SP) and calcitonin gene-related peptide (CGRP) (0.3-1 microM) increased, in a concentration-dependent manner, the basal secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) from cultured lymphocyte-enriched mononuclear cells isolated from human peripheral blood. SP and CGRP (0.1 microM) synergistically increased basal TNF alpha secretion. Dynorphin A((1-17)) (0.1-1 microM) did not modify basal cytokine secretion. Lipopolysaccharide (10 ng/ml)-induced cytokine secretion and [(3)H]thymidine uptake were not altered by any neuropeptide (at 0.1 microM). Thus, SP and CGRP stimulate the production of pro-inflammatory cytokines from lymphocytes only at high concentrations, similar to those reached during tissue damage.
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PMID:Substance P and calcitonin gene-related peptide increase IL-1 beta, IL-6 and TNF alpha secretion from human peripheral blood mononuclear cells. 1179 59

Orofacial pain frequently originates from pathologic conditions in the masticatory muscles or temporomandibular joints (TMJs). The mediators and mechanisms that monitor pain and inflammation, centrally or peripherally, are of great interest in the search for new treatment modalities. The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) have all been found at high levels in the synovial fluid of arthritic TMJs in association with spontaneous pain, while serotonin (5-HT) has been found in association with hyperalgesia/allodynia of the TMJ. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) have been found in arthritic TMJs, but not in healthy TMJs, in association with hyperalgesia/allodynia of the TMJ as well as spontaneous pain. Anterior open bite, which may be a clinical sign of TMJ destruction, has been found in association with high levels of CGRP, NPY, and IL-1 beta in the synovial fluid of the TMJ. Interleukin-1 beta has also been related to radiographic signs of joint destruction. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are both present in the arthritic TMJ, and PGE2 has been shown to be associated with hyperalgesia/allodynia of the TMJ. Very little is known about pain and inflammatory mediators in muscles. However, we know that 5-HT and PGE2 are involved in the development of pain and hyperalgesia/allodynia of the masseter muscle in patients with fibromyalgia, whereas local myalgia (myofascial pain) seems to be modulated by other, as yet unknown mediators. Interaction between the peripheral nervous system (sensory and sympathetic nerves), the immune system, and local cells is probably of great importance for the modulation of pain and inflammation in the TMJ and orofacial musculature.
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PMID:Neuroendocrine, immune, and local responses related to temporomandibular disorders. 1188 48


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