title: A possible role for interleukin 37 in the pathogenesis of Behcet's disease.
abstract: Interleukin 37 has been found to play a significant regulatory role in the innate immune response. It is not yet known whether IL-37 has also been involved in the development of Behcet's disease (BD), a chronic systemic inflammatory disease. To examine the role of IL-37 in the pathogenesis of BD, a number of experiments were performed. IL-37 expression in peripheral blood mononuclear cells (PBMCs) from BD patients and normal controls was measured by RT-PCR and flow cytometry. Monocyte-derived Dendritic Cells (DCs) were cultured with or without IL-37 and levels of cytokines in the culture supernatants were measured by ELISA. The DC surface markers, reactive oxygen species (ROS) production and mitogen-activated protein kinase (MAPK) activation were measured by flow cytometry. The effect of IL-37-treated DCs on the development of CD4(+) T cells was measured by ELISA and flow cytometry. The results show that both IL-37 mRNA level and protein expression were significantly decreased in PBMCs from active BD patients compared to normal controls. DCs stimulated with rIL-37 showed a decreased expression of IL-6, IL-1β and TNF-α, and a higher production of IL-27. rIL-37 significantly inhibited the production of ROS by DCs and reduced the activation of ERK1/2, JNK and P38 MAPK in DCs. rIL-37-treated DCs remarkably inhibited Th17 and Th1 cell responses as compared to control DCs. rIL-37 did not affect the expression of DC surface markers (CD40, CD86, CD80 and HLA-DR) or IL-10 production by DCs. We conclude that a decreased IL-37 expression in active BD patients may trigger the production of pro-inflammatory cytokines and ROS in association with activation of Th1 and Th17 cells by DCs.
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Kijlstra
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400016, P.R. China. peizengycmu@126.com.
authors.forename: P
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C508587:IL37 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D017382:Reactive Oxygen Species