C‑C chemokine receptor type 3 gene knockout alleviates inflammatory responses in allergic rhinitis model mice by regulating the expression of eosinophil granule proteins and immune factors

Abstract

The present study aimed to investigate the effects of C-C chemokine receptor type 3 (CCR3) gene knockout on allergic rhinitis (AR) in mice, as well as the underlying molecular mechanisms. Ovalbumin was administrated to CCR3+/+ and CCR3−/− BALB/c mice to establish an AR model. The mice were divided into four groups: i) Normal control (CG), ii) AR model (AR), iii) CCR3 knockout CG (CCR3−/−CG) and iv) AR model with CCR3 knockout (CCR3−/−AR). Histological sections of nasal mucosae were examined by hematoxylin and eosin staining, which revealed that CCR3 knockout suppressed the invasion of inflammatory cells and relieved the damage of nasal mucosae. Peripheral blood smear and nasal-washing smears were evaluated by Wright's staining. Eosinophil (EOS) numbers in nasal mucosae, peripheral blood, and nasal washings of the various groups were ranked in the order: AR>CCR3−/−AR>CG>CCR3−/−. mRNA expression levels of CCR3, EOS peroxidase (EPO), EOS cationic protein (ECP), and major basic protein (MBP) in the peripheral serum and nasal washings were detected by reverse transcription-polymerase chain reaction. Interferon-γ (IFN-γ), interleukin (IL)-4, IL-10, and immunoglobulin E (IgE) protein levels in the peripheral serum and nasal washings were investigated by ELISA. CCR3 mRNA expression was not detected in the CCR3−/− and CCR3−/−AR groups, whereas expression levels in the AR group were markedly higher compared with expression in the CG group. Compared with the CG-associated groups (i.e., the CG and CCR3−/−CG groups), the levels of EPO, ECP, MBP, IL-4, and IgE were significantly increased in the AR-associated groups (that is, R and CCR3−/−AR). In addition, the CCR3−/−AR group mice produced significantly lower levels of EPO, ECP, MBP, IL-4 and IgE compared with the AR group, whereas the expression levels of IFN-γ and IL-10 were increased. CCR3 gene knockout may alleviate EOS invasion and the inflammatory response in AR model mice by reducing the expression levels of EPO, ECP, MBP, IL-4, and IgE, and increasing the expression of IL-10 and IFN-γ.

C-C Motif Chemokine Receptor 3-Mediated Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase Signaling: Promising Targets for Human Airway Epithelial Mucin 5AC Induction by Eotaxin-2 and Eotaxin-3

“…Inhibitory effects of a CCR3 antagonist on the eotaxin/CCR3 chemotactic response indicate the key role of the CCR3 pathway in eosinophil chemotaxis [17]. CCR3 knockout has been reported to alleviate eosinophil infiltration and the inflammatory response in an allergic rhinitis murine model [18]. Antagonizing CCR3 resulted in decreased nasal lavage ECP and symptom-relieving effects after allergen challenge, suggesting the therapeutic potential of CCR3-targeting pharmacological interventions for eosinophil-induced allergic inflammation [19].…”

CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes

“…To our knowledge a link between CCR3 and S100A12 remains uncharacterized; however, activation of CCR3 is able to drive the expression of a number of pro-inflammatory pathways ( Zhu et al., 2018 ) and therefore it is possible that CCR3 may act directly or indirectly on S100A12, although this would need to be directly examined in future mechanistic studies. It is also important to note that when we knocked down levels of CCR3 in OA FLS derived from patients with high SF CCL22 levels, we did not observe an impact on S100A12 expression.…”

Use of Nasal Cytology in Diagnosis of Sinonasal Disorders

“…The cytoplasm is of variable color from orange to intense pink, very distinctive and unmistakable. Inside, small granules are observed that contain substances such as the major basic protein (MBP), the eosinophilic cationic protein, and the eosinophilic peroxidase [9]. These substances have a cytotoxic and antibacterial function.…”