Alternatively activated macrophages express the IL-27 receptor alpha chain WSX-1
IMMUNOBIOLOGY
Authors: Rueckerl, Dominik; Hessmann, Manuela; Yoshimoto, Takayuki; Ehlers, Stefan; Hoelscher, Christoph
Abstract
The interleukin (IL)-27 receptor-alpha WSX-1 is one component of the heterodimeric IL-27 receptor that is expressed on various cell types including macrophages. We previously demonstrated that IL-27 induces STAT-3 and is able to inhibit the production of pro-inflammatory cytokines in activated macrophages suggesting a novel feed-back mechanism by which IL-27 can modulate excessive inflammation. Because IL-4 receptor-alpha (IL-4R alpha)-induced alternatively activated macrophages have also been described to attenuate pathological inflammatory immune responses, we analyzed the contribution of IL-27 in alternative macrophage activation. In the present study, like IL-10 and IL-4, IL-27 was found to suppress IL-12/23p4O production in activated bone marrow-derived macrophages. Whereas IL-10 induced the upregulation of the IL-4R alpha on macrophages, receptor expression was not triggered by IL27. In contrast to IL-4, IL-27 did not induce alternative macrophage activation but IL-4 strongly upregulated the expression of WSX-1 on macrophages and alternative macrophage activation enhanced IL-27-mediated signalling. We therefore conclude from our study that IL-10, IL-4 and IL-27 collaborate in modulating macrophage activation by successive upregulation of the IL-4R alpha and WSX-1 on alternatively activated macrophages. (c) 2006 Elsevier GmbH. All rights reserved.
Association between polymorphisms in IL27 gene and renal cell carcinoma
BIOMARKERS
Authors: Pu, Yan; Chen, Peng; Zhou, Bin; Zhang, Peng; Wang, Yanyun; Song, Yaping; Zhang, Lin
Abstract
Context: Interleukin-27 is a new member of the IL-12 family which plays an important role in human carcinogenesis. Objective: To investigate whether polymorphisms in IL27 contribute to renal cell carcinoma (RCC) risk. Materials and methods: These two polymorphisms were genotyped in 329 RCC patients and 386 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Significantly increased RCC risk was associated the G allele of both rs153109 and rs17855750 (rs153109: p = 0.006, OR = 1.364, 95% CI = 1.095-1.700; rs17855750: p = 0.001, OR = 1.768, 95% CI = 1.245-2.511). Conclusion: The present study provided evidence that rs153109 and rs17855750 were associated with increased risk for RCC, suggesting an important role IL-27 may play in nephrocarcinogenesis.