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- Abdelhadi, Saly, et al.
(författare)
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Expression of calcitonin gene-related peptide in atopic dermatitis and correlation with distress
- 2024
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Ingår i: Immunopharmacology and immunotoxicology. - : TAYLOR & FRANCIS LTD. - 0892-3973 .- 1532-2513. ; 46:1, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAtopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the expression of CGRP in the skin of patients with AD.MethodsTwenty-seven adult patients with AD, characterized with clinical and psychodemographic parameters, were investigated regarding CGRP expression in skin biopsies, using an immunohistochemical technique.ResultsThe total number of CGRP-positive nerve-like fibers was found to be higher in lesional skin than in non-lesional skin. Moreover, more inflammatory cells of dendritic shape intruded into the epidermis in lesional skin compared to non-lesional skin. Keratinocytes showing expression of CGRP were also found in lesional skin. Interestingly, the number of CGRP-positive nerve-like fibers in lesional skin correlated with depressive and anxiety scores. Correlation with depressive score was also found for round CGRP-positive inflammatory cells in the epidermis.ConclusionsCGRP may have a role in both the inflammatory process and distress, in AD.
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| 3. |
- Blom, Kristin, et al.
(författare)
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The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation
- 2017
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Ingår i: Immunopharmacology and immunotoxicology. - : Informa UK Limited. - 0892-3973 .- 1532-2513. ; 39:4, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation. The MBZ-induced gene expression signature in the promyeloblastic HL-60 cell line was strongly enriched in genes involved in monocyte/macrophage pro-inflammatory (M1) activation. This was subsequently validated using MBZ-treated THP-1 monocytoid cells that demonstrated gene expression, surface markers and cytokine release characteristic of the M1 phenotype. At high concentrations MBZ substantially induced the release of IL-1 beta and this was further potentiated by lipopolysaccharide (LPS). At low MBZ concentrations, cotreatment with LPS was required for MBZ-stimulated IL-1 beta secretion to occur. Furthermore, we show that the activation of protein kinase C, ERK1/2 and NF-kappaB were required for MBZ-induced IL-1 release. MBZ-induced IL-1 release was found to be dependent on NLRP3 inflammasome activation and to involve TLR8 stimulation. Finally, MBZ induced tumor-suppressive effects in a coculture model with differentiated THP-1 macrophages and HT29 colon cancer cells. In summary, we report that MBZ induced a pro-inflammatory (M1) phenotype of monocytoid cells, which may, at least partly, explain MBZ's anticancer activity observed in animal tumor models and in the clinic.
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| 6. |
- El-Nour, H, et al.
(författare)
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Study of innervation, sensory neuropeptides, and serotonin in murine contact allergic skin
- 2005
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Ingår i: Immunopharmacology and immunotoxicology. - 0892-3973 .- 1532-2513. ; 27:1, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- Density of nerve fibers, axonal growth, calcitonin gene-related peptide (CGRP), and substance P, and serotonin immunoreactivity as well as concentration were all determined in a murine model of contact allergy. Female Balb/c mice were sensitized on the back with oxazolone and 6 days later challenged with the same antigen on the dorsal surface of the ears, while control mice received the vehicle only. Then, 24 hr postchallenge, one ear was processed for immunohistochemical staining, while the other was frozen and processed for gas chromatography-mass spectrometry or radioimmunoassay (RIA). Protein gene product 9.5 (PGP 9.5) positive nerve fibers showed a tendency to increase in inflamed ears versus control ears in epidermis as well as the dermis. Growth-associated protein-43 (GAP-43) positive fibers in the epidermis were increased (p < .01) in inflamed ears, compared with control ears, as was the case for the dermal fibers, indicating increased axonal growth. Total (epidermis and dermis) numbers of CGRP and substance P positive nerve fibers tended to increase in the inflamed skin in contrast to control skin. In contrast, RIA demonstrated a lower (p < .05) concentration of CGRP in the inflamed ears compared with controls and a tendency for substance P to decrease in concentration in eczematous ears versus controls. There was no difference in serotonin concentration, or in the number of serotonin positive mast cells, between the inflamed and control skin, whereas semiquantification of serotonin positive platelets showed an increase in the inflamed (++) compared with control ears (+). Our results indicate that 24 hr after being challenged with the antigen, at the peak of murine skin inflammation, axonal growth, sensory neuropeptides, as well as serotonin may be involved. Copyright © 2005 Taylor & Francis Inc.
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| 9. |
- Lonndahl, Louise, et al.
(författare)
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Decreased innervation of eczematous skin in NC/Nga atopic mice during chronic mild stress
- 2010
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Ingår i: IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY. - : Informa UK Limited. - 0892-3973 .- 1532-2513. ; 32:1, s. 147-152
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Tidskriftsartikel (refereegranskat)abstract
- Material and methods: We used three groups of mice, stressed control (SC, stressed but not immunized with a mite antigen), non-stressed eczematous (NSE, not stressed but immunized) and stressed eczematous (SE, stressed and immunized). Results: There was a decrease of protein gene product (PGP) 9.5 positive nerve fibers in SE compared to SC mice, in both epidermis and dermis, also in SE compared to NSE mice. Also a decrease in growth associated protein (GAP)-43 positive nerve fibers was seen in SE compared to SC, in both epidermis and dermis. Conclusion: Chronic mild stress in atopic mice leads to decreased innervation in eczematous lesions.
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| 10. |
- Lonndahl, L, et al.
(författare)
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Tachykinin upregulation in atopic dermatitis
- 2019
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Ingår i: Immunopharmacology and immunotoxicology. - : Informa UK Limited. - 1532-2513 .- 0892-3973. ; 41:1, s. 117-122
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Tidskriftsartikel (refereegranskat)
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