Volume 43 Issue 8
Jul.  2022
Turn off MathJax
Article Contents
Tongxin YANG, Guang WANG, Rui XU, Siwei SU, Kewei FANG, Jianhe LIU, Jiongming LI. Effect of Cathelicidin LL-37 on Transmembrane Barrier Function of Urothelial Cells[J]. Journal of Kunming Medical University, 2022, 43(8): 34-40. doi: 10.12259/j.issn.2095-610X.S20220806
Citation: Tongxin YANG, Guang WANG, Rui XU, Siwei SU, Kewei FANG, Jianhe LIU, Jiongming LI. Effect of Cathelicidin LL-37 on Transmembrane Barrier Function of Urothelial Cells[J]. Journal of Kunming Medical University, 2022, 43(8): 34-40. doi: 10.12259/j.issn.2095-610X.S20220806

Effect of Cathelicidin LL-37 on Transmembrane Barrier Function of Urothelial Cells

doi: 10.12259/j.issn.2095-610X.S20220806
  • Received Date: 2022-04-20
    Available Online: 2022-07-23
  • Publish Date: 2022-07-28
  •   Objective  To explore the specific effect of LL-37 on the destruction of the transmembrane barrier function of bladder urothelial cells and develop a cellular experimental model suitable for studying interstitial cystitis (IC) in vitro.   Methods   Human urothelial immortalized cells SV-HUC-1 were treated with LL-37 at different concentrations. The transepithelial electrical resistance (TEER) was measured by a transepithelial resistor, and the cell proliferative activity was detected by CCK-8 kit. Cell cycle and calcium ion concentration were detected by flow cytometry. The expression levels of heparan sulfate, a key component of glycosaminoglycan (GAGs), were detected by RT-qPCR and WB.   Results   In vitro measurement showed that 100 and 200 μg/mL of LL-37 significantly inhibited the TEER and destroyed the transmembrane barrier function of SV-HUC-1. The CCK-8 test and PI staining flow cytometry results showed that LL-37 above 100 μg/mL could significantly reduce the proliferation activity of SV-HUC-1 and increase the proportion of SV-HUC-1 in the G0/G1 phase (P < 0.05), suggesting that cell proliferation was significantly inhibited. Further flow cytometry analysis showed that the calcium ion concentration in SV-HUC-1treated with LL-37 was significantly increased (P < 0.05), and the increase was related to LL-37 concentration. RT-qPCR and WB assays confirmed significant up-regulation of heparan sulfate, a key GAGs component, in the LL-37-treated SV-HUC-1 (P < 0.05).   Conclusion   The cathelicidin LL-37 can inhibit the expression of GAGs and destroy the cell proliferation and transmembrane barrier function of SV-HUC-1.
  • loading
  • [1]
    Birder L A. Pathophysiology of interstitial cystitis[J]. International Journal of Urology, 2019, 26( Suppl 1): 12-15.
    [2]
    Marcu I,Campian E C,Tu F F. Interstitial cystitis/bladder pain syndrome[J]. Seminars in Reproductive Medicine,2018,36(2):123-135. doi: 10.1055/s-0038-1676089
    [3]
    Daniels A M,Schulte A R,Herndon C M. Interstitial cystitis:An update on the disease process and treatment[J]. Journal of Pain & Palliative Care Pharmacotherapy,2018,32(1):49-58.
    [4]
    Theoharides T C, Kempuraj D, Sant G R. Mast cell involvement in interstitial cystitis: A review of human and experimental evidence[J]. Urology, 2001, 57(6 Suppl 1): 47-55.
    [5]
    Sahiner I F,Soylu H,Ates E,et al. Impact of intravesical hyaluronic acid treatment on bladder inflammation in interstitial cystitis rat model[J]. International Brazilian Journal of Urology,2018,44(5):1014-1022. doi: 10.1590/s1677-5538.ibju.2017.0713
    [6]
    Jia W,Schults A J,Jensen M M,et al. Bladder pain in an LL-37 interstitial cystitis and painful bladder syndrome model[J]. American Journal of Clinical and Experimental Urology,2017,5(2):10-17.
    [7]
    Johansson J,Gudmundsson G H,Rottenberg M E,et al. Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37[J]. The Journal of Biological Chemistry,1998,273(6):3718-3724. doi: 10.1074/jbc.273.6.3718
    [8]
    Martin Jensen M,Jia W,Schults A J,et al. IL-33 mast cell axis is central in LL-37 induced bladder inflammation and pain in a murine interstitial cystitis model[J]. Cytokine,2018,110(30):420-427.
    [9]
    王光,杨童欣,姜永明,等. 抗菌肽LL-37诱导大鼠膀胱壁肥大细胞的炎症反应[J]. 昆明医科大学学报,2019,40(6):5.
    [10]
    Nijnik A,Hancock R E. The roles of cathelicidin LL-37 in immune defences and novel clinical applications[J]. Current Opinion in Hematology,2009,16(1):41-47. doi: 10.1097/MOH.0b013e32831ac517
    [11]
    Oottamasathien S, Jia W, McCoard L, et al. A murine model of inflammatory bladder disease: Cathelicidin peptide induced bladder inflammation and treatment with sulfated polysaccharides[J]. The Journal of Urology, 2011, 186(4 Suppl): 1684-1692.
    [12]
    Oottamasathien S, Jia W, Roundy L M, et al. Physiological relevance of LL-37 induced bladder inflammation and mast cells[J]. The Journal of Urology, 2013, 190(4 Suppl): 1596-1602.
    [13]
    Howard P S,Renfrow D,Schechter N M,et al. Mast cell chymase is a possible mediator of neurogenic bladder fibrosis[J]. Neurourology and Urodynamics,2004,23(4):374-382. doi: 10.1002/nau.20032
    [14]
    Lee W Y,Savage J R,Zhang J,et al. Prevention of anti-microbial peptide LL-37-induced apoptosis and ATP release in the urinary bladder by a modified glycosaminoglycan[J]. PloS One,2013,8(10):77854. doi: 10.1371/journal.pone.0077854
    [15]
    Song Y J,Cao J Y,Jin Z,et al. Inhibition of microRNA-132 attenuates inflammatory response and detrusor fibrosis in rats with interstitial cystitis via the JAK-STAT signaling pathway[J]. Journal of Cellular Biochemistry,2019,120(6):9147-9158. doi: 10.1002/jcb.28190
    [16]
    Xie J,Liu B,Chen J,et al. Umbilical cord-derived mesenchymal stem cells alleviated inflammation and inhibited apoptosis in interstitial cystitis via AKT/mTOR signaling pathway[J]. Biochemical and Biophysical Research Communications,2018,495(1):546-552. doi: 10.1016/j.bbrc.2017.11.072
    [17]
    Boudieu L,Mountadem S,Lashermes A,et al. Blocking α(2)δ-1 subunit reduces bladder hypersensitivity and inflammation in a cystitis mouse model by decreasing NF-kB pathway activation[J]. Frontiers in Pharmacology,2019,10(1):133.
    [18]
    Assi K,Pillai R,Gómez-Muñoz A,et al. The specific JNK inhibitor SP600125 targets tumour necrosis factor-alpha production and epithelial cell apoptosis in acute murine colitis[J]. Immunology,2006,118(1):112-121. doi: 10.1111/j.1365-2567.2006.02349.x
    [19]
    Henderson N C,Pollock K J,Frew J,et al. Critical role of c-jun (NH2) terminal kinase in paracetamol- induced acute liver failure[J]. Gut,2007,56(7):982-990. doi: 10.1136/gut.2006.104372
    [20]
    Zhao J,Wang L,Dong X,et al. The c-Jun N-terminal kinase (JNK) pathway is activated in human interstitial cystitis (IC) and rat protamine sulfate induced cystitis[J]. Scientific Reports,2016,6(1):19670. doi: 10.1038/srep19670
  • Relative Articles

    [1] Lizhu ZHAO, Ying DONG, Yue DENG, Lihua YANG. Correlation between Epithelial Cell Related Genes and Prognosis of Patients with Ovarian Cancer based on Single Cell Sequencing. Journal of Kunming Medical University, 2024, 45(4): 9-16.  doi: 10.12259/j.issn.2095-610X.S20240402
    [2] Guozhu LIANG, Shimei RUAN, Yanmei HE, Hailong YANG. Prospects of Antimicrobial Peptides as Immunomodulators in the Treatment of Bacterial Infections. Journal of Kunming Medical University, 2023, 44(10): 189-195.  doi: 10.12259/j.issn.2095-610X.S20231013
    [3] Fang SUN, Shiying HUANG, Shu LIU, Jingyun FU. Association between Glucose Time in Range and Carotid Artery Intima-media Thickness in Type-2 Diabetes Mellitus. Journal of Kunming Medical University, 2023, 44(4): 48-52.  doi: 10.12259/j.issn.2095-610X.S20230427
    [4] Yindong HE, Jun ZHANG, Hua HUANG, Ruming LIU, Xi WANG. Glucose Transport in Human Placenta and the Effect of GDM on Placental Glucose Transport. Journal of Kunming Medical University, 2022, 43(9): 160-165.  doi: 10.12259/j.issn.2095-610X.S20220903
    [5] Luo Dan , Yang Cheng Gang . . Journal of Kunming Medical University, 2020, 41(09): 12-16.
    [6] Li Jing , Lei Wen , Deng Shu Hao , Fan Du , Pu Ling , Yang Dong Mei , Zhao Xiao Yuan , Li Yang , Dong Zhao Xing . . Journal of Kunming Medical University, 2019, 40(01): 10-13.
    [7] Jiang Yu , Qian Wei Min , Ye Ling , Ning Jing , Li Jian Min . . Journal of Kunming Medical University, 2019, 40(04): 57-60.
    [8] Wang Guang , Yang Tong Xin , Jiang Yong Ming , Fang Ke Wei , Liu Jian He , Li Jiong Ming . . Journal of Kunming Medical University, 2019, 40(06): 23-27.
    [9] Feng Da Ying , Li Ting , Wang Xiao Dong , Chen Zhi Wei , Wang Hai Ting , Ye Shuang . . Journal of Kunming Medical University, 2018, 39(11): 56-61.
    [10] Tang Ying . . Journal of Kunming Medical University, 2015, 36(08): 1-1.
    [11] Kui Li Yue . . Journal of Kunming Medical University,
    [12] Tai Wen Lin . . Journal of Kunming Medical University,
    [13] Jin Di . . Journal of Kunming Medical University,
    [14] Zhan Hui . . Journal of Kunming Medical University,
    [15] Li Jie . . Journal of Kunming Medical University,
    [16] Gao Zhen Hua . . Journal of Kunming Medical University,
    [17] Yuan Cong . . Journal of Kunming Medical University,
    [18] Li Si Man . The Antimicrobial Activity of Snake Venom Antimicrobial Peptide Cathelicidin on E. coli. Journal of Kunming Medical University,
    [19] . The Preparation of Chitosans Membranes with Different Molecular Weight. Journal of Kunming Medical University,
    [20] . Inducing Differentiation of Pig's Bone Mesenchymal Stem Cell(BMSC) to Urothelial Epithelia in Vitro. Journal of Kunming Medical University,
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(2)  / Tables(1)

    Article Metrics

    Article views (3624) PDF downloads(42) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return