Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats

Santoni, Giorgio; Perfumi, Marina; Spreghini, Elisabetta; Romagnoli, Stefano; Piccoli, Mario

doi:10.1016/s0165-5728(98)00173-8

Cited by 30 publications

(36 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thymocytes express NK1Rs (Santoni et al, 1999). Indeed, SP augments the proliferation of CD4 + T cells in the presence of mitogens, including human T cells (Payan et al, 1984); this effect is abolished in the presence of the NK1R blocker SR140333 [(S)1-2- [3-(3,4- (Santoni et al, 1999). These pharmacological actions are in accord with the presence of mRNA for NK1R in human T cells (see Bost, 2004).…”

Section: E Transient Receptor Potential Channels In Obesity and Metamentioning

confidence: 87%

“…This possibility notwithstanding, a more likely explanation is depletion by capsaicin of neuronal SP since exogenous SP is able to fully restore antibody response to sheep red blood cell antigens and prevent capsaicin-induced apoptosis in T cells (Santoni et al, 1996(Santoni et al, , 2004. Thymocytes express NK1Rs (Santoni et al, 1999). Indeed, SP augments the proliferation of CD4 + T cells in the presence of mitogens, including human T cells (Payan et al, 1984); this effect is abolished in the presence of the NK1R blocker SR140333 [(S)1-2- [3-(3,4- (Santoni et al, 1999).…”

Section: E Transient Receptor Potential Channels In Obesity and Metamentioning

confidence: 99%

See 1 more Smart Citation

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

2014

View full text Add to dashboard Cite

Section: E Transient Receptor Potential Channels In Obesity and Metamentioning

confidence: 87%

Section: E Transient Receptor Potential Channels In Obesity and Metamentioning

confidence: 99%

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

2014

View full text Add to dashboard Cite

“…SP is capable of directly augmenting T cell-mediated immune responses (23,24). SP stimulates the proliferation of T lymphocytes (38), enhanced IL-2 production (39), and expression of T lymphocyte activation Ags such as IL-2 receptor ␣-chain (CD25) and RT1B MHC class II molecule (40). Released SP may also modulate ACD responses by acting on macrophages and APCs (41-43).…”

Section: Discussionmentioning

confidence: 99%

Neutral Endopeptidase Terminates Substance P-Induced Inflammation in Allergic Contact Dermatitis

Scholzen

Steinhoff

Bonaccorsi

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

Sensory nerve-derived neuropeptides such as substance P demonstrate a number of proinflammatory bioactivities, but less is known about their role in inflammatory skin disease. The cell surface metalloprotease neutral endopeptidase (NEP) is the principal proteolytic substance P-degrading enzyme. This study tests the hypothesis that the absence of NEP results in dysregulated inflammatory skin responses. The effector phase of allergic contact dermatitis (ACD) responses was examined in NEP−/− knockout and NEP+/+ wild-type mice and compared with the irritant contact dermatitis response in these animals. NEP was found to be normally immunolocalized in epidermal keratinocytes and dermal blood vessels. The ACD ear swelling response was 2.5-fold higher in animals lacking NEP and was accompanied by a significant increase in plasma extravasation and infiltration of inflammatory leukocytes. The augmented ACD response in NEP−/− animals was abrogated by either administration of a neurokinin receptor 1 antagonist or by repeated pretreatment with topical capsaicin. Similar to NEP−/− mice, the acute inhibition of NEP in NEP+/+ animals resulted in an augmented ACD response. In contrast to the ACD responses, little differences were observed in the irritant contact dermatitis response of NEP−/− compared with NEP+/+ animals after epicutaneous application of the skin irritants croton oil or SDS. Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD.

show abstract

“…[1][2][3][4][5][6] Many of the acute cellular and physiologic effects associated with CPS exposure are mediated by vanilloid receptors that can act as voltage-independent channels. 7 Vanilloid receptors are expressed mainly by primary sensory neurons involved in nociception and neurogenic inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22][23]25,28,29,33,34 We have previously reported that neonatal CPS treatment results in marked reduction of thymus weight and cellularity, impaired thymocyte proliferation in response to T-cell mitogens and apoptotic cell death. 4,5 These effects are partly dependent on the ability of CPS to induce substance P depletion by rat thymus. However, a direct action of CPS on thymocytes has not been explored so far nor the receptor(s) mediating these CPS-induced effects.…”

Section: Introductionmentioning

confidence: 99%

Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death

et al. 2004

View full text Add to dashboard Cite

Herein, we provide the first evidence on the capsaicin (CPS) receptor vanilloid receptor type-1 (VR1) by rat thymocytes, and its involvement in CPS-induced apoptosis. VR1 mRNA was identified by quantitative RT-PCR in CD5 þ thymocytes. By immunofluorescence and flow cytometry, we found that a substantial portion of CD5 þ thymocytes, namely CD4 þ and double negative (DN) cell subsets, express VR1 that was present on plasma membrane on discrete spots. By Western blot, VR1 protein was identified as a single band of 95 kDa. We also described that CPS could trigger two distinct pathways of thymocyte death, namely apoptosis and necrosis depending on the dose of CPS exposure. CPS-induced apoptosis involved intracellular free calcium (Ca 2 þ ) influx, phosphatidylserine exposure, mitochondrial permeability transmembrane pore (PTP) opening and mitochondrial transmembrane potential (DW m ) dissipation leading to cytochrome c release, activation of caspase-9 and -3 and oligonucleosomal DNA fragmentation. VR1 was functionally implicated in these events as they were completely abrogated by the VR1 antagonist, capsazepine (CPZ). Finally, we demonstrated that VR1 expression on distinct thymocytes was associated with the selective ability of CPS to trigger DNA fragmentation in VR1 þ CD4 þ and DN thymocytes. Overall, our results suggest that the expression of VR1 on thymocytes may function as a sensor of harmful stimuli present in the thymic environment.

show abstract

Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats

Cited by 30 publications

References 51 publications

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

Neutral Endopeptidase Terminates Substance P-Induced Inflammation in Allergic Contact Dermatitis

Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death

Contact Info

Product

Resources

About