Gene Symbol: TMED1
Description: transmembrane p24 trafficking protein 1
Alias: IL1RL1LG, Il1rl1l, Tp24, p24g1, transmembrane emp24 domain-containing protein 1, IL1RL1-binding protein, interleukin 1 receptor-like 1 ligand, p24 family protein gamma-1, transmembrane emp24 protein transport domain containing 1
Species: human
Products:     TMED1

Top Publications

  1. Gayle M, Slack J, Bonnert T, Renshaw B, Sonoda G, Taguchi T, et al. Cloning of a putative ligand for the T1/ST2 receptor. J Biol Chem. 1996;271:5784-9 pubmed
    ..In searching for a ligand for T1/ST2, we have cloned a cell surface protein to which it binds. This protein is unable to initiate signal transduction by the T1/ST2 receptor in several in vitro assays. ..
  2. Wilson S, Jones F, Fofana H, Landoure A, Kimani G, Mwatha J, et al. A late IL-33 response after exposure to Schistosoma haematobium antigen is associated with an up-regulation of IL-13 in human eosinophils. Parasite Immunol. 2013;35:224-8 pubmed publisher
    ..IL-33 may play an important downstream role in the human response to schistosome adult worm antigen exposure. ..
  3. Boudaud M, Turcotte S, Stankova J, Rola Pleszczynski M. IL-33 Upregulates Cysteinyl Leukotriene Receptor Type 1 Expression in Human Peripheral Blood CD4+ T Lymphocytes. J Immunol. 2018;201:2787-2798 pubmed publisher
  4. Mueller T, Jaffe A. Soluble ST2--analytical considerations. Am J Cardiol. 2015;115:8B-21B pubmed publisher
  5. Beltrán C, Núñez L, Díaz Jiménez D, Farfan N, Candia E, Heine C, et al. Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16:1097-107 pubmed publisher
    ..The novel association between the ST2/IL-33 system and IBD seems to identify that variations in this axis might regulate the inflammatory process in these diseases. ..
  6. Tominaga S, Tago K, Tsuda H, Komine M. Dual function of IL-33 on proliferation of NIH-3T3 cells. Cytokine. 2015;72:105-8 pubmed publisher
    ..The negative effect of IL-33 on cell proliferation is a novel finding and would provide an important clue to the roles of IL-33 and ST2/ST2L in growth regulation. ..
  7. Holmes D, Yeh J, Yan D, Xu M, Chan A. Dusp5 negatively regulates IL-33-mediated eosinophil survival and function. EMBO J. 2015;34:218-35 pubmed publisher
    ..In addition, Dusp5(-/-) eosinophils demonstrate enhanced IL-33-mediated activation and effector functions. Together, these data support a role for DUSP5 as a novel negative regulator of IL-33-dependent eosinophil function and survival. ..
  8. Stampalija T, Chaiworapongsa T, Romero R, Tarca A, Bhatti G, Chiang P, et al. Soluble ST2, a modulator of the inflammatory response, in preterm and term labor. J Matern Fetal Neonatal Med. 2014;27:111-21 pubmed publisher
    ..Decreased concentrations of sST2 in IAI are likely to promote a pro-inflammatory response, which is important for parturition in the context of infection. ..
  9. Pascual Figal D, Januzzi J. The biology of ST2: the International ST2 Consensus Panel. Am J Cardiol. 2015;115:3B-7B pubmed publisher
    ..In contrast, sST2 acts as a decoy receptor and, by sequestering IL-33, antagonizes the cardioprotective effects of IL-33/ST2L interaction. ..

More Information


  1. Yang S, Lin J, Wu S, Huang K, Jung F, Ma M, et al. Membrane translocation of IL-33 receptor in ventilator induced lung injury. PLoS ONE. 2015;10:e0121391 pubmed publisher
    ..Moreover, IL-33/ST2 signaling activated by mechanically responsive lung injury may potentially serve as a new therapy target. ..
  2. Zhao J, Wei J, Bowser R, Traister R, Fan M, Zhao Y. Focal adhesion kinase-mediated activation of glycogen synthase kinase 3β regulates IL-33 receptor internalization and IL-33 signaling. J Immunol. 2015;194:795-802 pubmed publisher
    ..These results suggest that modulation of the ST2L internalization by FAK/GSK3β might serve as a unique strategy to lessen pulmonary inflammation. ..
  3. Chen W, Hong J, Gannon J, Kakkar R, Lee R. Myocardial pressure overload induces systemic inflammation through endothelial cell IL-33. Proc Natl Acad Sci U S A. 2015;112:7249-54 pubmed publisher
    ..Our study reveals that endothelial cell secretion of IL-33 is crucial for translating myocardial pressure overload into a selective systemic inflammatory response. ..
  4. Wu L, Luo Z, Zheng J, Yao P, Yuan Z, Lv X, et al. IL-33 Can Promote the Process of Pulmonary Fibrosis by Inducing the Imbalance Between MMP-9 and TIMP-1. Inflammation. 2018;41:878-885 pubmed publisher
    ..IL-33 can regulate deposition of ECM and promote the process of pulmonary fibrosis by inducing the imbalance between MMP-9 and TIMP-1. ..
  5. Matsumoto K, Kouzaki H, Kikuoka H, Kato T, Tojima I, Shimizu S, et al. Soluble ST2 suppresses IL-5 production by human basophilic KU812 cells, induced by epithelial cell-derived IL-33. Allergol Int. 2018;67S:S32-S37 pubmed publisher
    ..Epithelial cell-derived IL-33 promoted IL-5 production by KU812 cells. The subsequently produced sST2 has important roles in regulating Th2 responses. ..
  6. Lü J, Kang J, Zhang C, Zhang X. The role of IL-33/ST2L signals in the immune cells. Immunol Lett. 2015;164:11-7 pubmed publisher
    ..Understanding the specific role of IL-33/ST2L in different immune cells will help to answer the remaining questions that are important for diseases pathologies and intervention strategies by targeting the IL-33/ST2L signals. ..
  7. Gao Q, Li Y, Li M. The potential role of IL-33/ST2 signaling in fibrotic diseases. J Leukoc Biol. 2015;98:15-22 pubmed publisher
    ..In this review, the biologic characteristics of IL-33 and the role of the IL-33/ST2 signaling pathway in various fibrotic diseases will be discussed. We hope this overview will provide new insights for the treatment of these diseases. ..
  8. Januzzi J, Mebazaa A, Di Somma S. ST2 and prognosis in acutely decompensated heart failure: the International ST2 Consensus Panel. Am J Cardiol. 2015;115:26B-31B pubmed publisher
    ..The role of sST2 measurement in acutely decompensated heart failure evaluation and management will be discussed. ..
  9. Zhang Y, Zhang C, Zhuang R, Ma Y, Zhang Y, Yi J, et al. IL-33/ST2 correlates with severity of haemorrhagic fever with renal syndrome and regulates the inflammatory response in Hantaan virus-infected endothelial cells. PLoS Negl Trop Dis. 2015;9:e0003514 pubmed publisher
    ..Our results indicate that the IL-33 acts as an initiator of the "cytokine storm" during HTNV infection, while sST2 can inhibit this process. Our findings could provide a promising immunotherapeutic target for the disease control. ..
  10. Dattagupta A, Immaneni S. ST2: Current status. Indian Heart J. 2018;70 Suppl 1:S96-S101 pubmed publisher
    ..sup>2 The ligand of ST2 is Interleukin-33 (IL-33), which is involved in reducing fibrosis and hypertrophy in mechanically strained tissues.3. ..
  11. Veeraveedu P, Sanada S, Okuda K, Fu H, Matsuzaki T, Araki R, et al. Ablation of IL-33 gene exacerbate myocardial remodeling in mice with heart failure induced by mechanical stress. Biochem Pharmacol. 2017;138:73-80 pubmed publisher
    ..These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF. ..
  12. Akimoto M, Takenaga K. Role of the IL-33/ST2L axis in colorectal cancer progression. Cell Immunol. 2018;: pubmed publisher
    ..At any rate, recent studies have provided overwhelming evidence that the IL-33/ST2L axis plays important roles in CRC progression. This review summarizes the role of the IL-33/ST2L axis in the UC and CRC microenvironments. ..
  13. Queiroz G, Costa R, Alcantara Neves N, Nunes de Oliveira Costa G, Barreto M, Carneiro V, et al. IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population. Int J Immunogenet. 2017;44:51-61 pubmed publisher
    ..tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma. ..
  14. Yndart A, Kaushik A, Agudelo M, Raymond A, Atluri V, Saxena S, et al. Investigation of Neuropathogenesis in HIV-1 Clade B and C Infection Associated with IL-33 and ST2 Regulation. ACS Chem Neurosci. 2015;6:1600-12 pubmed publisher
    ..This led to neuroinflammation which dysregulates synaptic function and apoptosis. These parameters are common in neuroAIDS provoked by HIV infection. ..
  15. De la Fuente M, MacDonald T, Hermoso M. The IL-33/ST2 axis: Role in health and disease. Cytokine Growth Factor Rev. 2015;26:615-23 pubmed publisher
    ..The IL-33/ST2 axis is involved in the pathogenesis of atopic and autoimmune diseases, cancer, and central nervous system disorders. Here, we review recent findings on the role of the IL-33/ST2 axis in health and disease. ..
  16. He B, Zheng L, Zhou H, He Y, Chen Z, Xiao S, et al. Dynamic observation of IL-33 and its receptors in HIV patients who received HAART. Cell Mol Biol (Noisy-le-grand). 2017;63:73-77 pubmed publisher
    ..Serum IL-33 and sST2 levels, and CD4+ST2L+ expression in PBMCs are closely associated with HIV-1 infection and immune reconstitution in patients received HAART. ..
  17. Bonyadi Rad E, Musumeci G, Pichler K, Heidary M, Szychlinska M, Castrogiovanni P, et al. Runx2 mediated Induction of Novel Targets ST2 and Runx3 Leads to Cooperative Regulation of Hypertrophic Differentiation in ATDC5 Chondrocytes. Sci Rep. 2017;7:17947 pubmed publisher
    ..Runx3 was, furthermore, identified as a novel Runx2 target in chondrocytes. This study suggests that Runx2 mediates ST2 and Runx3 induction to cooperatively regulate hypertrophic differentiation of ATDC5 chondrocytes. ..
  18. Liao B, Cao P, Zeng M, Zhen Z, Wang H, Zhang Y, et al. Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps. Allergy. 2015;70:1169-80 pubmed publisher
    ..The positive feedback loop between TSLP, IL-33 and their receptors, and Th2 cytokines may facilitate Th2-skewed inflammation in eosinophilic CRSwNP. ..
  19. Shelite T, Liang Y, Wang H, Mendell N, Trent B, Sun J, et al. IL-33-Dependent Endothelial Activation Contributes to Apoptosis and Renal Injury in Orientia tsutsugamushi-Infected Mice. PLoS Negl Trop Dis. 2016;10:e0004467 pubmed publisher
    ..This study indicates a pathogenic role of alarmin IL-33 in a murine model of scrub typhus and highlights infection-triggered EC damage and IL-33-mediated pathological changes during the course of Orientia infection. ..
  20. O Donnell C, Mahmoud A, Keane J, Murphy C, White D, Carey S, et al. An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer. Br J Cancer. 2016;114:37-43 pubmed publisher
    ..This was associated with a decrease in macrophage infiltration, with IL-33-induced macrophage recruitment reduced by antagonising CCL2 in vitro. The IL-33/ST2 signalling axis may have a protective role in colon carcinogenesis. ..
  21. Ariyoshi W, Okinaga T, Chaweewannakorn W, Akifusa S, Nisihara T. Mechanisms involved in enhancement of matrix metalloproteinase-9 expression in macrophages by interleukin-33. J Cell Physiol. 2017;232:3481-3495 pubmed publisher
    ..These results indicate an essential role of ERK/CREB and NF-?B cascades in the induction of MMP-9 in monocytes/macrophages through AP-1 activation. ..
  22. Funakoshi Tago M, Miyagawa Y, Ueda F, Mashino T, Moriwaki Y, Tago K, et al. A bis-malonic acid fullerene derivative significantly suppressed IL-33-induced IL-6 expression by inhibiting NF-?B activation. Int Immunopharmacol. 2016;40:254-264 pubmed publisher
    ..These results suggest that the bis-malonic fullerene derivative has potential as a specific drug for the treatment of IL-33-induced inflammatory diseases by specifically inhibiting the NF-?B activation pathway. ..
  23. Du H, Fu H, Li D, Qiao Y, Wang Q, Liu W. The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway. J Interferon Cytokine Res. 2016;36:552-62 pubmed publisher
    ..In conclusion, IL-33 is closely interlinked in AD skins and keratinocytes. IL-33 plays an important role in the pathogenesis of immune inflammatory responses in AD, which might be a possible therapeutic target in the treatment of AD. ..
  24. Fursov N, Lu J, Healy C, Wu S, Lacy E, Filer A, et al. Monoclonal antibodies targeting ST2L Domain 1 or Domain 3 differentially modulate IL-33-induced cytokine release by human mast cell and basophilic cell lines. Mol Immunol. 2016;75:178-87 pubmed publisher
  25. Granne I, Southcombe J, Snider J, Tannetta D, Child T, Redman C, et al. ST2 and IL-33 in pregnancy and pre-eclampsia. PLoS ONE. 2011;6:e24463 pubmed publisher
    ..These results suggest that sST2 may play a significant role in pregnancies complicated by pre-eclampsia and increased sST2 could contribute to the type 1 bias seen in this disorder. ..
  26. Traister R, Uvalle C, Hawkins G, Meyers D, Bleecker E, Wenzel S. Phenotypic and genotypic association of epithelial IL1RL1 to human TH2-like asthma. J Allergy Clin Immunol. 2015;135:92-9 pubmed publisher
    ..Both pathologic and genetic approaches support a role for IL1RL1 in severe asthma, as well as TH2-lke asthma, suggesting that targeting this pathway may have therapeutic benefits. ..
  27. Biton J, Khaleghparast Athari S, Thiolat A, Santinon F, Lemeiter D, Hervé R, et al. In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis. J Immunol. 2016;197:1708-19 pubmed publisher
    ..Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development. ..
  28. Wagner A, Köhm M, Nordin A, Svenungsson E, Pfeilschifter J, Radeke H. Increased Serum Levels of the IL-33 Neutralizing sST2 in Limited Cutaneous Systemic Sclerosis. Scand J Immunol. 2015;82:269-74 pubmed publisher
    ..Therefore, we not only like to propose sST2 as a biomarker for progressive vascular fibrosis, but moreover, suggest that the involvement of sST2 in the pathogenesis of lcSSc may be exploited therapeutically. ..
  29. Akimoto M, Maruyama R, Takamaru H, Ochiya T, Takenaga K. Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment. Nat Commun. 2016;7:13589 pubmed publisher
    ..In conclusion, we show that sST2 negatively regulates tumour growth and the metastatic spread of CRC through modification of the tumour microenvironment. Thus, the IL-33/ST2L axis may be a potential therapeutic target in CRC. ..
  30. Wang C, Dong C, Xiong S. IL-33 enhances macrophage M2 polarization and protects mice from CVB3-induced viral myocarditis. J Mol Cell Cardiol. 2017;103:22-30 pubmed publisher
    ..Additionally, IL-4 neutralization abolished the IL-33-mediated cardiac functional improvement in myocarditis mice. Collectively, our findings provide a novel therapeutic role for IL-33 in CVB3-induced myocarditis. ..
  31. Marzullo A, Ambrosi F, Inchingolo M, Manca F, Devito F, Angiletta D, et al. ST2L Transmembrane Receptor Expression: An Immunochemical Study on Endarterectomy Samples. PLoS ONE. 2016;11:e0156315 pubmed publisher
    ..Considering our data, we hypothesize that ST2L/IL33 axis could drive the mechanism of plaque development and eventually rupture. ..
  32. Bergis D, Kassis V, Radeke H. High plasma sST2 levels in gastric cancer and their association with metastatic disease. Cancer Biomark. 2016;16:117-25 pubmed publisher
    ..Soluble ST2 is associated with advanced and metastatic disease in GC patients and significantly correlates with the duration of the disease. The IL-33/sST2 ratio may offer a new, interesting approach in identifying GC patients. ..
  33. Ohta S, Tago K, Funakoshi Tago M, Matsugi J, Yanagisawa K. Intracellular NF-HEV/IL-33 harbors essential roles in Ras-induced cellular transformation by contributing to cyclin D1 protein synthesis. Cell Signal. 2016;28:1025-36 pubmed publisher
    ..We showed that Ras (G12V)-induced cyclin D1 protein synthesis was markedly suppressed by the knockdown of IL-33. Taken together, the results of the present study strongly suggest a novel role for IL-33 in cellular transformation. ..
  34. Peng H, Zhang Q, Li X, Liu Z, Shen J, Sun R, et al. IL-33 Contributes to Schistosoma japonicum-induced Hepatic Pathology through Induction of M2 Macrophages. Sci Rep. 2016;6:29844 pubmed publisher
    ..japonicum infection. These data demonstrate that IL-33 contributes to hepatic granuloma pathology through induction of M2 macrophages during S. japonicum infection. ..
  35. Gao Y, Ma L, Luo C, Wang T, Zhang M, Shen X, et al. IL-33 Exerts Neuroprotective Effect in Mice Intracerebral Hemorrhage Model Through Suppressing Inflammation/Apoptotic/Autophagic Pathway. Mol Neurobiol. 2017;54:3879-3892 pubmed publisher
    ..In conclusion, IL-33 provides neuroprotection through suppressing inflammation, apoptotic, and autophagic activation in collagenase-induced ICH model. ..
  36. Ragusa R, Cabiati M, Guzzardi M, D Amico A, Giannessi D, Del Ry S, et al. Effects of obesity on IL-33/ST2 system in heart, adipose tissue and liver: study in the experimental model of Zucker rats. Exp Mol Pathol. 2017;102:354-359 pubmed publisher
    ..The strong relationships with NP systems and inflammatory mediators could suggest an involvement for IL-33/ST2 in molecular pathways leading to cardiac dysfunction and inflammation associated with obesity. ..
  37. Connolly D, O Neill L, McGettrick A. The GOLD domain-containing protein TMED1 is involved in interleukin-33 signaling. J Biol Chem. 2013;288:5616-23 pubmed publisher
    ..Here, we show that TMED1 associates with ST2L...
  38. Díaz Jiménez D, Núñez L, De la Fuente M, Dubois Camacho K, Sepulveda H, Montecino M, et al. A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis. Sci Rep. 2017;7:10180 pubmed publisher
    ..Our data indicate that IL1RL1 SNPs rs6543115(C) confer susceptibility to UC and is contained in the GRE, which may modulate glucocorticoid-induced sST2 expression. ..
  39. Wang M, Shen G, Xu L, Liu X, Brown J, Feng D, et al. IL-1 receptor like 1 protects against alcoholic liver injury by limiting NF-?B activation in hepatic macrophages. J Hepatol. 2017;: pubmed publisher
  40. Tago K, Ohta S, Kashiwada M, Funakoshi Tago M, Matsugi J, Tominaga S, et al. ST2 gene products critically contribute to cellular transformation caused by an oncogenic Ras mutant. Heliyon. 2017;3:e00436 pubmed publisher
    ..Our current study strongly suggests the importance of ST2 gene products in cellular transformation, and the presence of novel mechanism how ST2 gene products affect the cellular transformation and cell proliferation...
  41. Basith S, Manavalan B, Govindaraj R, Choi S. In silico approach to inhibition of signaling pathways of Toll-like receptors 2 and 4 by ST2L. PLoS ONE. 2011;6:e23989 pubmed publisher
    ..Our predicted oligomeric signaling models may provide a basis for the understanding of the assembly process of TIR domain interactions, which has thus far proven to be difficult via in vivo studies. ..
  42. Tare N, Li H, Morschauser A, Cote Sierra J, Ju G, Renzetti L, et al. KU812 cells provide a novel in vitro model of the human IL-33/ST2L axis: functional responses and identification of signaling pathways. Exp Cell Res. 2010;316:2527-37 pubmed publisher
    ..KU812 represents the first human cell line-based in vitro model of the IL-33/ST2L axis and provides a valuable tool to aid in understanding the mechanism and significance of IL-33 and ST2L interaction and function. ..
  43. Jenne N, Frey K, Brugger B, Wieland F. Oligomeric state and stoichiometry of p24 proteins in the early secretory pathway. J Biol Chem. 2002;277:46504-11 pubmed
    ..In addition, we show differential cycling of individual p24 members. These data point to a complex and dynamic system of altering dimerizations of the family members. ..
  44. Chan W, Pejnovic N, Lee C, Al Ali N. Human IL-18 receptor and ST2L are stable and selective markers for the respective type 1 and type 2 circulating lymphocytes. J Immunol. 2001;167:1238-44 pubmed
    ..Therefore, these cell surface molecules could serve as important determinants of the immune status of human diseases in general, and thereby could be useful for therapeutic monitoring and intervention. ..
  45. Dominguez M, Dejgaard K, Fullekrug J, Dahan S, Fazel A, Paccaud J, et al. gp25L/emp24/p24 protein family members of the cis-Golgi network bind both COP I and II coatomer. J Cell Biol. 1998;140:751-65 pubmed
    ..Surprisingly, upon expression of mutated members, steady-state distribution of unmutated ones shifted as well, presumably as a consequence of their observed oligomeric properties. ..