Browsing by Author "Wang, Tie"
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- ItemOpen AccessIdentification of multiple isoforms of glucocorticoid receptor in nasal polyps of patients with chronic rhinosinusitis(2022-06-11) Shao, Shan; Wang, Yue; Zhao, Yan; Xu, Yuan; Wang, Tie; Du, Kun; Bao, Shiping; Wang, Xiangdong; Zhang, LuoAbstract Background The conventional belief that glucocorticosteroid (GC) acts through a single brand glucocorticoid receptor (GR)α protein has changed dramatically with the discovery of multiple GR isoforms. We aimed to evaluate whether multiple GR protein isoforms are expressed in chronic rhinosinusitis with nasal polyps (CRSwNP) and whether GR protein isoform expression profiles differ between different endotypes of CRSwNP. Methods Thirty-eight patients with CRSwNP and ten healthy volunteers were included. The protein expression of multiple GR isoforms in nasal polyps (NPs) tissue and control mucosae was examined by western blot analysis with different GR antibodies. Results Five bands, including three bands for known proteins (GRα-A/B, GRα-C, and GRα-D) and two bands for unidentified proteins at 67 kilodaltons (kDa) and 60 kDa, were identified with both total GR antibody (PA1-511A) and GRα-specific antibody (PA1-516). GRα-D intensity, which was abundant in nasal mucosa, was significantly increased in the CRSwNP group and was especially elevated in the noneosinophilic CRSwNP (NE-CRSwNP) group (PA1-511A: P < 0.001 and P = 0.0018; PA1-516: P < 0.003 and P = 0.006, respectively). Additionally, the intensities of the newly recognized 67 kDa and 60 kDa bands were much greater in the NE-CRSwNP subgroup than in the eosinophilic CRSwNP (E-CRSwNP) subgroup; in the E-CRSwNP subgroup, the median intensities were even lower than those in the control group. Conclusions This study provides evidence that nasal tissues express multiple GR protein isoforms. GR protein isoforms presented disease and tissue-specific expression profiles that differed between the CRSwNP and control groups and between the E-CRSwNP and NE-CRSwNP subgroups. Graphical abstract
- ItemOpen AccessRoles of Endothelial Toll-like Receptor (TLR) 4 in Neutrophil Recruitment During Experimental Colitis(2017) Wang, Tie; Waterhouse, Christopher Curns; Xue, Yingwei; MacNaughton, Wallace Keith; McKay, Derek Mark; Sun, WenjingThe innate immune system uses pattern recognition receptors (PRRs) encoded by germline genes of the host to detect danger signals from damaged tissues as well as conserved microbial “molecular patterns” called damage- or pathogen-associated molecular patterns (DAMPs or PAMPs). PRRs are essential for the initiation of immune responses. Among PRRs, Toll-like Receptor (TLR) 4 has gained a great deal of attention, as it is the first discovered PRR, and it is the receptor for lipopolysaccharide (LPS, a major cell wall component of Gram-negative bacteria). It has been demonstrated that TLR4 has many roles in the pathogenesis of inflammatory bowel diseases (IBD) and experimental colitis. However, the functions of endothelial TLR4 remain unclear. In this thesis, we hypothesized that endothelial TLR4 provokes neutrophil recruitment in the colon during experimental colitis. Endothelial TLR4 is upregulated during dextran sulfate sodium (DSS)-induced colitis, in part by tumor necrosis factor (TNF)-α. The upregulation of endothelial TLR4 occurs prior to neutrophil recruitment in DSS colitis. Loss of endothelial TLR4 attenuates the histological damage in DSS-induced colitis. Mice lacking endothelial TLR4 have fewer colonic neutrophils during DSS colitis. Mice with a specific deletion of endothelial TLR4 have a decreased number of adherent neutrophils in the microcirculation of their colon upon DSS challenge. NanoString nCounter CodeSet analysis showed endothelial intercellular adhesion molecule (ICAM) 2 has lower expression in mice lacking endothelial TLR4, measured by immunofluorescence and flow cytometry. In vitro cultured endothelial cells respond to LPS challenge to increase the expression of ICAM2. Blocking of ICAM2 also inhibits neutrophil adhesion in DSS colitis. In conclusion, endothelial TLR4 is an active player in experimental colitis and mediates neutrophil recruitment.