关键词: Allergic asthma CCL2/CCR2 signaling pathway Inflammatory monocytes Th1-associated cytokines Th2 inflammatory responses

Mesh : Animals Antibodies / pharmacology Asthma / chemically induced drug therapy immunology pathology Cell Movement / drug effects immunology Chemokine CCL2 / antagonists & inhibitors immunology Mice Monocytes / immunology pathology Ovalbumin / toxicity Receptors, CCR2 / antagonists & inhibitors immunology Signal Transduction / drug effects immunology Th1 Cells / immunology pathology Th2 Cells / immunology pathology

来  源:   DOI:10.1016/j.imlet.2019.08.006   PDF(Sci-hub)

Abstract:
Recent studies have reported recruitment of inflammatory monocytes by cytokines including chemokine (C-C motif) ligand 2 (CCL2) are critical in allergic responses. We aimed to investigate the role of inflammatory monocytes and CCL2 in mouse model with ovalbumin (OVA)-induced allergic asthma. Mice were sensitized with OVA to induce allergic asthma. The proportion of inflammatory cells in bronchoalveolar lavage fluid (BALF) and peritoneal lavage fluid (PLF) were measured by flow cytometry. The expression of CCL2 and CCL2 receptor (CCR2) were determined by qPCR and western blot. The concentrations of Type 1 helper T (Th1) and Type 2 helper T (Th2) cytokines in PLF were detected by ELISA. Inflammatory monocytes are recruited in PLF, and expression of CCL2 and CCR2 were elevated in OVA-induced mice. In addition, transfer of CCR2 knockdown inflammatory monocytes decreased the levels of allergic asthma biomarkers. Injection of anti-CCL2 or anti-CCR2 antibody decreased the proportion of eosinophils and inflammatory monocytes in BALF. Blockade of CCL2/CCR2 signaling pathway suppressed the allergen-induced Th2 cytokines and enhanced the levels of Th1-associated cytokines. Blockade of CCL2/CCR2 signaling pathway in sensitization-recruited inflammatory monocytes exhibits protective effects in mouse model of OVA-induced allergic asthma by inhibiting the Th2 inflammatory responses.
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