Background Abatacept (Aba) is a cytotoxic T-lymphocyte antigen-4 and fragment crystallizable fusion protein. Aba blocks B7/Cluster of differentiation 28 - cytotoxic T-lymphocyte antigen-4 costimulatory pathway, inhibits cluster of differentiation 4+ T-cell activation, and is used as an anti-inflammatory drug. Objectives We conducted this study to assess the effectiveness of Aba in the treatment of allergic rhinitis (AR) in a mouse model. Methods We divided 40 four-week-old BALB/c mice into four groups: control group ( n = 10), positive control group (AR, n = 10), Aba group (AR + Aba, n = 10), and dexamethasone group (AR + Dex, n = 10). Mice in each group were challenged intranasally with daily ovalbumin (OVA) administration. Episodes of sneezing and nose rubbing were counted. Mice were sacrificed on day 42 and cytokines were measured in nasal lavage fluid. Nasal mucosae of five mice from each group were used for reverse transcriptase-polymerase chain reaction and western blot assay. Samples were collected from five mice from each group for histological analysis. Results Symptoms of AR significantly improved in the AR + Aba and AR + Dex groups compared with the AR group. Fewer eosinophils and goblet cells were seen in the AR + Aba and AR + Dex groups compared with the AR group. Both the AR + Aba and AR + Dex groups showed a significant decrease in nasal T helper 2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13 and T cell activation related IL-17A, and interferon gamma (IFN- γ). Total immunoglobulin (Ig) E and OVA-specific IgG1 levels were also significantly lower in the AR + Aba and AR + Dex groups. OVA-specific IgE level was also significantly lower in the AR + Aba than AR group. Conclusions Aba suppresses allergic inflammation and appears to be a good treatment for AR.
Background and Objectives A recent study revealed that calcitonin gene-related protein (CGRP) plays an important role in inflammatory airway diseases. However, the influence of CGRP on chronic rhinosinusitis (CRS) has not been studied. This study investigated the expression, activity, and potential pathogenic role of CGRP in patients with CRS with nasal polyposis (CRSwNP).Subjects and Method Patients with CRSwNP and control subjects were enrolled. The CRSwNP group was divided according to the presence of eosinophilic polyps and non-eosinophilic polyps. Nasal polyps (NPs) and uncinate tissues (UTs) from patients with CRSwNP and UTs from control subjects were obtained to investigate the expression of α-/β-CGRP and chromogranin A. In addition, the expression patterns of cytokines following exposure to exogenous CGRP were analyzed in dispersed nasal polyp cells (DNPCs) from patients with eosinophilic or non-eosinophilic CRSwNP. The effects of CGRP on lipopolysaccharide (LPS)-induced nuclear factor-kappa light chain enhancer of activated B cells (NF-κB) signaling change were evaluated in THP-1 cells.Results The expression of α-/β-CGRP and number of CGRP-producing cells were significantly higher in NPs from patients with CRSwNP than in UTs from controls. Exogenous CGRP decreased the expression of inflammatory cytokines and increased that of the anti-inflammatory cytokines in DNPCs from patients with eosinophilic nasal polyps (EPs) and also increased the expression of tissue remodeling-related and anti-inflammatory cytokines in DNPCs from patients with non-eosinophilic nasal polyps (N-EPs). CGRP inhibited the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) phosphorylation and NF-κB translocation in LPS-stimulated M1 macrophages.Conclusion CGRP expression in NPs may play a significant role in nasal polypogenesis through inflammatory modulation, and it could be a future target to modulate certain aspects of CRSwNP.
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