Tumor necrosis factor-alpha and Fas/Fas ligand signaling pathways in chronic spontaneous urticaria

• Published in: Allergy, asthma, and clinical immunology Vol. 15; no. 1; pp. 15 - 9
• Main Authors: Grzanka, R., Damasiewicz-Bodzek, A., Kasperska-Zajac, A.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.03.2019; BioMed Central; BMC
• Subjects: Apoptosis; Arthritis; Chronic spontaneous urticaria; Cytokines; Dermatitis; Disease; Enzyme-linked immunosorbent assay; Enzymes; Hives (Disease); Inflammation; Inflammatory diseases; Ligands; Necrosis; Soluble Fas (sFas); Soluble Fas ligand (sFasL); Soluble tumor necrosis factor receptor type 1 (sTNF-R1); Soluble tumor necrosis factor receptor type 2 (sTNF-R2); TNF inhibitors; Tumor necrosis factor; Tumor necrosis factor alpha (TNF-α); Tumor necrosis factor-TNF; Tumors; Urticaria; United States > US; Chronic spontaneous urticaria; Tumor necrosis factor alpha (TNF-α); Soluble tumor necrosis factor receptor type 1 (sTNF-R1); Soluble Fas ligand (sFasL); Soluble Fas (sFas); Soluble tumor necrosis factor receptor type 2 (sTNF-R2)
• ISSN: 1710-1492; 1710-1484; 1710-1492
• DOI: 10.1186/s13223-019-0332-7

There is increasing evidence pointing to the important role of tumor necrosis factor-alpha (TNF-α), a key inflammatory and apoptotic mediator in urticarial inflammation. However, the role of the TNF-α system and Fas/Fas ligand (FasL) in the apoptosis-inducing pathways in chronic spontaneous urticaria (CSU), remain unclear. To determine circulating concentrations of TNF-α, soluble TNF-α receptor type 1 and type 2 (sTNF-R1 and sTNF-R2, respectively) as well as soluble Fas (sFas) and FasL (sFasL) in CSU subjects. Serum TNF-α, sTNF-R1, sTNF-R2, sFas, sFasL concentrations were measured using enzyme-linked immunosorbent assay in CSU subjects and in the healthy subjects. TNF-α concentrations were significantly higher in CSU subjects and moderate-to-severe CSU than in the controls, while there were no significant differences in TNF-α concentrations between subjects with mild CSU and the controls. sTNF-R1 and sTNF-R2 concentrations were significantly higher in all CSU and moderate-severe CSU subjects vs. the controls. Serum concentrations were also significantly higher in mild CSU vs. the controls, but not in moderate-severe CSU vs. mild CSU. No significant differences were observed in sFas and sFasL concentrations between CSU subjects and the healthy controls. Significant correlations were found between concentrations of TNF-α and its receptors, as well as sTNF-R1 and sTNF-R2, but not with the urticaria activity score (UAS). There was no relationship between TNF-α/sTNF-R1/sTNF-R2 and sFas/sFasL pathways in CSU. CSU is associated with the activation of the TNF-α/receptors signaling pathway, marked by increased circulating concentrations of TNF-α, sTNF-R1 and sTNF-R2, which are related to each other in this disease. In contrast, the circulating sFas/FasL system is not up-regulated in CSU, and sFas/sFasL may not be a useful marker of the activity/severity of urticarial processes. Considering the lack of significant changes in sFas/sFasL (mainly reflecting systemic apoptosis) in CSU patients, it appears that elevated serum TNF-α concentrations are related to its pro-inflammatory function rather than an enhanced systemic apoptotic response in CSU.