IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis

被引:4
作者
Moniruzzaman, Md. [1 ,2 ]
Wong, Kuan Yau [1 ,2 ]
Wang, Ran [1 ,2 ]
Symon, Hamish [2 ]
Mueller, Alexandra [1 ,2 ]
Rahman, M. Arifur [1 ,2 ]
Hasnain, Sumaira Z. [1 ,2 ,3 ]
机构
[1] Univ Queensland, Fac Med, Brisbane, Qld 4072, Australia
[2] Univ Queensland, Mater Res Inst, Translat Res Inst, Immunopathol Grp, Brisbane, Qld 4102, Australia
[3] Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld 4072, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
IL-20; epithelial cells; colitis; goblet cells; ERK1; 2; endoplasmic reticulum stress; IL-22; RECEPTOR COMPLEXES; EXPRESSION; STRESS;
D O I
10.3390/ijms24010174
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cytokine Interleukin (IL)-20 belongs to the IL-10 superfamily. IL-20 levels are reported to increase in the intestines of Ulcerative Colitis (UC) patients, however not much is known about its effects on intestinal epithelial cells. Here, we investigated the influence of IL-20 on intestinal epithelial cell lines and primary intestinal organoid cultures. By using chemical-induced (dextran sodium sulphate; DSS) colitis and a spontaneous model of colitis (Winnie mice), we assess whether recombinant IL-20 treatment is beneficial in reducing/improving pathology. Following stimulation with IL-20, intestinal primary organoids from wild-type and Winnie mice increased the expression of ERK1/2. However, this was lost when cells were differentiated into secretory goblet cells. Importantly, IL-20 treatment significantly reduced endoplasmic reticulum (ER) stress, as measured by spliced-XBP1 in epithelial cells, and this effect was lost in the goblet cells. IL-20 treatment in vivo in the DSS and Winnie models had minimal effects on pathology, but a decrease in macrophage activation was noted. Taken together, these data suggest a possible, but subtle role of IL-20 on epithelial cells in vivo. The therapeutic potential of IL-20 could be harnessed by the development of a targeted therapy or combination therapy to improve the healing of the mucosal barrier.
引用
收藏
页数:12
相关论文
共 26 条
[1]   Expression of IL-24, an Activator of the JAK1/STAT3/SOCS3 Cascade, Is Enhanced in Inflammatory Bowel Disease [J].
Andoh, Akira ;
Shioya, Makoto ;
Nishida, Atsushi ;
Bamba, Shigeki ;
Tsujikawa, Tomoyuki ;
Kim-Mitsuyama, Shokei ;
Fujiyama, Yoshihide .
JOURNAL OF IMMUNOLOGY, 2009, 183 (01) :687-695
[2]  
Bech Rikke, 2016, Mol Cell Ther, V4, P1
[3]   Expression of IL-24 and IL-24 receptors in human wound tissues and the biological implications of IL-24 on keratinocytes [J].
Bosanquet, David C. ;
Harding, Keith G. ;
Ruge, Fiona ;
Sanders, Andrew J. ;
Jiang, Wen G. .
WOUND REPAIR AND REGENERATION, 2012, 20 (06) :896-903
[4]   Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins [J].
Das, Indrajit ;
Png, Chin Wen ;
Oancea, Iulia ;
Hasnain, Sumaira Z. ;
Lourie, Rohan ;
Proctor, Martina ;
Eri, Rajaraman D. ;
Sheng, Yong ;
Crane, Denis I. ;
Florin, Timothy H. ;
McGuckin, Michael A. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (06) :1201-1216
[5]   Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types [J].
Dumoutier, L ;
Leemans, C ;
Lejeune, D ;
Kotenko, SV ;
Renauld, JC .
JOURNAL OF IMMUNOLOGY, 2001, 167 (07) :3545-3549
[6]   Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis [J].
Eichele, Derrick D. ;
Kharbanda, Kusum K. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2017, 23 (33) :6016-6029
[7]   IL-10-and IL-20-Expressing Epithelial and Inflammatory Cells are Increased in Patients with Ulcerative Colitis [J].
Fonseca-Camarillo, Gabriela ;
Furuzawa-Carballeda, Janette ;
Llorente, Luis ;
Yamamoto-Furusho, Jesus K. .
JOURNAL OF CLINICAL IMMUNOLOGY, 2013, 33 (03) :640-648
[8]   The epithelial-specific ER stress sensor ERN2/IRE1β enables host-microbiota crosstalk to affect colon goblet cell development [J].
Grey, Michael J. ;
De Luca, Heidi ;
Ward, Doyle V. ;
Kreulen, Irini A. M. ;
Gwilt, Katlynn Bugda ;
Foley, Sage E. ;
Thiagarajah, Jay R. ;
McCormick, Beth A. ;
Turner, Jerrold R. ;
Lencer, Wayne I. .
JOURNAL OF CLINICAL INVESTIGATION, 2022, 132 (17)
[9]   High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22 [J].
Gulhane, Max ;
Murray, Lydia ;
Lourie, Rohan ;
Tong, Hui ;
Sheng, Yong H. ;
Wang, Ran ;
Kang, Alicia ;
Schreiber, Veronika ;
Wong, Kuan Yau ;
Magor, Graham ;
Denman, Stuart ;
Begun, Jakob ;
Florin, Timothy H. ;
Perkins, Andrew ;
Cuiv, Paraic O. ;
McGuckin, Michael A. ;
Hasnain, Sumaira Z. .
SCIENTIFIC REPORTS, 2016, 6
[10]   Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress [J].
Hasnain, Sumaira Z. ;
Borg, Danielle J. ;
Harcourt, Brooke E. ;
Tong, Hui ;
Sheng, Yonghua H. ;
Ng, Choa Ping ;
Das, Indrajit ;
Wang, Ran ;
Chen, Alice C-H ;
Loudovaris, Thomas ;
Kay, Thomas W. ;
Thomas, Helen E. ;
Whitehead, Jonathan P. ;
Forbes, Josephine M. ;
Prins, Johannes B. ;
McGuckin, Michael A. .
NATURE MEDICINE, 2014, 20 (12) :1417-1426