Search

Ticks are blood-feeding ectoparasites that transmit a variety of pathogens to host animals and humans, causing severe infectious diseases such as Lyme disease. In a certain combination of animal and tick species, tick infestation elicits acquired immunity against ticks in the host, which can reduce the ability of ticks to feed on blood and to transmit pathogens in the following tick infestations. Therefore, our understanding of the cellular and molecular mechanisms of acquired tick resistance (ATR) can advance the development of anti-tick vaccines to prevent tick infestation and tick-borne diseases. Basophils are a minor population of white blood cells circulating in the bloodstream and are rarely observed in peripheral tissues under steady-state conditions. Basophils have been reported to accumulate at tick-feeding sites during re-infestation in cattle, rabbits, guinea pigs and mice. Selective ablation of basophils resulted in a loss of ATR in guinea pigs and mice, illuminating the essential role of basophils in the manifestation of ATR. In this review, we discuss the recent advance in the elucidation of the cellular and molecular mechanisms underlying basophil recruitment to the tick-feeding site and basophil-mediated ATR., (© 2020 The Authors. Parasite Immunology published by John Wiley & Sons Ltd.)

Objective: IgG4-related disease (IgG4-RD) is a unique inflammatory disorder in which Th2 cytokines promote IgG4 production. In addition, recent studies have implicated the Toll-like receptor (TLR) pathway. This study was undertaken to examine the expression of TLRs in salivary glands (SGs) from patients with IgG4-RD., Methods: SGs from 15 patients with IgG4-RD, 15 patients with Sjögren's syndrome (SS), 10 patients with chronic sialadenitis, and 10 healthy controls were examined histologically. TLR family gene expression (TLR-1 through TLR-10) was analyzed by DNA microarray in the submandibular glands (SMGs). Up-regulation of TLRs was confirmed in SGs from patients with IgG4-RD. Finally, the phenotype of human TLR-7 (huTLR-7)-transgenic C57BL/6 mice was assessed before and after stimulation with TLR agonist., Results: In patients with IgG4-RD, TLR-4, TLR-7, TLR-8, and TLR-9 were overexpressed. Polymerase chain reaction validated the up-regulation of TLR-7 in IgG4-RD compared with the other groups. Immunohistochemical analysis confirmed strong infiltration of TLR-7-positive cells in the SGs of patients with IgG4-RD. Double immunohistochemical staining showed that TLR-7 expression colocalized with CD163+ M2 macrophages. After in vitro stimulation with a TLR-7 agonist, CD163+ M2 macrophages produced higher levels of interleukin-33 (IL-33), which is a Th2-activating cytokine. In huTLR-7-transgenic mice, the focus and fibrosis scores in SMGs, pancreas, and lungs were significantly higher than those in wild-type mice (P < 0.05). Moreover, the concentration of serum IgG, IgG1, and IL-33 in huTLR-7-transgenic mice was distinctly increased upon stimulation with a TLR-7 agonist (P < 0.05)., Conclusion: TLR-7-expressing M2 macrophages may promote the activation of Th2 immune responses via IL-33 secretion in IgG4-RD., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Background and Purpose: Although oxaliplatin is an effective anti-cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although miRNAs have been increasingly recognized as important modulators in a variety of pain conditions, their involvement in chemotherapy-induced neuropathic pain is unknown., Experimental Approach: Oxaliplatin-induced chronic neuropathic pain was induced in rats by i.p. injections of oxaliplatin (2 mg·kg -1 ) for five consecutive days. The expression levels of miR-15b and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1 also known as β-secretase 1) were examined in the dorsal root ganglion (DRG). To examine the function of miR-15b, an adeno-associated viral vector encoding miR-15b was injected into the DRG in vivo., Key Results: Among the miRNAs examined in the DRG in the late phase of oxaliplatin-induced neuropathic pain, miR-15b was most robustly increased. Our in vitro assay results determined that BACE1 was a target of miR-15b. BACE1 and miR-15b were co-expressed in putative myelinated and unmyelinated DRG neurons. Overexpression of miR-15b in DRG neurons caused mechanical allodynia in association with reduced expression of BACE1. Consistent with these results, a BACE1 inhibitor dose-dependently induced significant mechanical allodynia., Conclusions and Implications: These findings suggest that miR-15b contributes to oxaliplatin-induced chronic neuropathic pain at least in part through the down-regulation of BACE1., (© 2016 The British Pharmacological Society.)

Background: The YKL-40 coding chitinase 3-like 1 gene is 1 of the most overexpressed genes in human glioblastomas. The objectives of this study were to explore YKL-40 protein expression status and World Health Organization (WHO) pathologic grades of primary human astrocytoma and to investigate the role of YKL-40 in the proliferation of both established and primary astrocytoma cells in vitro., Methods: WHO grade 1, 2, 3, and 4 primary astrocytomas (210 patients) were evaluated for YKL-40 protein expression status in immunohistochemical analyses. In addition, after transfection with a plasmid that contained YKL-40 small-interfering RNA (siRNA), cell proliferation and the cell cycle were measured with a cell-viability assay and flow cytometry. Expression levels of phosphorylated, total mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) were detected by Western blot analysis., Results: The percentage of positive cells and the staining intensity differed significantly between different pathologic tumor grades (P < .001). The YKL-40 immunoreactivity score increased markedly with increased pathologic grade (F = 18.89; P < .001). In the in vitro experiment, the cell cycle was arrested in G(1) phase. An inhibitor of the p38 MAPK, SB203580, could partially abrogate the cell proliferation inhibition effect by siRNA treatment. The expression levels of phosphorylated extracellular signal-regulated kinase 1/2 and phosphorylated AKT were notably decreased in siRNA-transfected U87 cells. In contrast, the expression levels of phosphorylated p38 and phosphorylated c-jun N-terminal kinase 1 and 2 increased significantly (P < .01)., Conclusions: YKL-40 expression status correlated well with the pathologic grade of primary astrocytomas. The current results also indicted that YKL-40 plays a pivotal role in glioma cell proliferation through activation of the MAPK and AKT pathways. YKL-40 may be an attractive target for glioma therapy., ((c) 2010 American Cancer Society.)